Devices and methods for cosmetic skin resurfacing

ABSTRACT

Disclosed herein are apparatuses, kits, and methods for treating skin, such as skin tightening, e.g., reducing skin laxity, for treating conditions that would benefit from tissue area or volume reduction, skin restoration, skin tightening, skin lifting, and/or skin repositioning, and/or for generally improving skin function or appearance. Such apparatuses, kits, and methods include one or more hollow needles each having at least one prong and a mechanism for removing skin tissue portion(s) from the hollow needle(s).

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. Ser. No.16/090,034 filed Sep. 28, 2018, which is a national stage application ofPCT Application No. PCT/US2017/024752, filed on Mar. 29, 2017, andclaims priority to U.S. Provisional Patent Application No. 62/314,748,filed on Mar. 29, 2016, all of which are incorporated herein in theirentirety by reference thereto.

BACKGROUND OF THE INVENTION

In aesthetic medicine, elimination of excess tissue and/or skin laxityis an important concern that affects more than 25% of the U.S.population. Conventional surgical therapies (e.g., a face lift, browlift, or breast lift) can be effective but are invasive, inconvenient,and expensive, while scarring limits the applicability of surgery tocertain treatment sites.

Although minimally invasive methods are available, such methods aregenerally less effective than surgical methods. For example, methodsusing energy sources (e.g., laser, non-coherent light, radiofrequency,and ultrasound) can be effective at improving the architecture andtexture of the skin but are less effective at tightening the skin orreducing skin laxity. In addition, tissue ablative methods that createmicro-ablations with photo-thermal energy can generate a coagulationzone in tissue that interferes with closure of the ablation zones,thereby inhibiting tissue tightening. These methods also require longerpatient healing times due to the biological reparative response tocoagulated and dead tissue during the remodeling process. Also, laserablation depth is typically limited by the depth of the laser beamfocus. Ablation of deeper tissue layers than is possible with availablelaser systems is desirable for the treatment of scars, for example.

Other methods, such as the use of neurotoxins, for example, botulinumtoxin, reduce the formation of dynamic wrinkles by paralysis of theinjected muscles, but such toxins have minimal or no direct effect onskin tightness or laxity. Finally, dermal fillers, such as hyaluronicacid, can be injected in the dermal layer to smooth out wrinkles andimprove contours, but such fillers do not directly tighten or reducelaxity of the skin. Thus, surgical therapies remain the gold standardfor lifting and/or tightening skin, as compared to energy-basedtechniques (e.g., laser, radiofrequency, and ultrasound) andinjection-based techniques (e.g., botulinum toxin and fillers such ashyaluronic acid- and collagen-based fillers).

Accordingly, there is a need for improved methods and devices thatprovide increased effectiveness over currently availableminimally-invasive techniques while maintaining convenience,affordability, and accessibility to patients desiring tissuerestoration.

SUMMARY OF THE INVENTION

This invention relates to hollow needles, needle assemblies, actuationunits, apparatuses, kits, and methods for cosmetic resurfacing of skintissue by removing portions of the skin tissue. The invention featuresan apparatus for generating a cosmetic effect in the skin tissue thatincludes one or more hollow needles each having at least one prong. Theapparatus may also include a mechanism for removing tissue portion(s)from the hollow needle(s).

In a first aspect, the invention features an apparatus for producing acosmetic effect in a skin tissue that includes at least one hollowneedle including at least a first prong provided at a distal end of thehollow needle, wherein an angle between a lateral side of the firstprong and a longitudinal axis of the hollow needle is at least about 20degrees, and wherein the hollow needle is configured to remove a portionof the skin tissue when the hollow needle is inserted into and withdrawnfrom the skin tissue. In some embodiments of the first aspect of theinvention, the angle between the lateral side of the first prong and thelongitudinal axis of the hollow needle is between about 20 and about 40degrees. In some embodiments, the angle between the lateral side of thefirst prong and the longitudinal axis of the hollow needle is about 30degrees.

In some embodiments of the first aspect of the invention, the hollowneedle further includes a second prong at the distal end of the hollowneedle. In some embodiments, an angle between the lateral side of thesecond prong and the longitudinal axis of the hollow needle is at leastabout 20 degrees. In some embodiments, the angle between the lateralside of the second prong and the longitudinal axis of the hollow needleis between about 20 and about 40 degrees. In some embodiments, thelateral side of the second prong and the longitudinal axis of the hollowneedle is about 30 degrees. In some embodiments, the angle between alateral side of the second prong and a longitudinal axis of the hollowneedle is less than about 20 degrees. In some embodiments, the anglebetween the lateral side of the second prong and the longitudinal axisof the hollow needle is between about 5 degrees and about 20 degrees.

In some embodiments, the first prong includes an edge. In someembodiments, each of the first and second prongs includes an edge.

In some embodiments, the first prong includes a flat tip. In someembodiments, each of the first and second prongs includes a flat tip. Insome embodiments, the flat tip has a length and a width. In someembodiments, the length and/or the width is at an angle relative to thelongitudinal axis of the hollow needle. In some embodiments, the lengthand/or the width is perpendicular to the longitudinal axis of the hollowneedle.

In a second aspect, the invention features an apparatus for producing acosmetic effect in a skin tissue that includes at least one hollowneedle including at least a first prong provided at a distal end of thehollow needle, wherein the first prong includes a flat tip having atleast two dimensions, and wherein the hollow needle is configured toremove a portion of the skin tissue when the hollow needle is insertedinto and withdrawn from the skin tissue.

In some embodiments of the second aspect of the invention, the hollowneedle further includes a second prong at the distal end of the hollowneedle. In some embodiments, the second prong includes a flat tip.

In some embodiments, the flat tip has a length and a width. In someembodiments, the length and/or the width is at an angle relative to thelongitudinal axis of the hollow needle. In some embodiments, the lengthand/or the width is perpendicular to the longitudinal axis of the hollowneedle.

In some embodiments of the second aspect of the invention, an anglebetween a lateral side of the first prong and a longitudinal axis of thehollow needle is at least about 20 degrees. In some embodiments, theangle between the lateral side of the first prong and the longitudinalaxis of the hollow needle is between about 20 and about 40 degrees. Insome embodiments, the angle between the lateral side of the first prongand the longitudinal axis of the hollow needle is about 30 degrees. Insome embodiments of the second aspect of the invention, an angle betweena lateral side of the first prong and a longitudinal axis of the hollowneedle is less than about 20 degrees. In some embodiments, the anglebetween the lateral side of the first prong and the longitudinal axis ofthe hollow needle is between about 5 degrees and about 20 degrees.

In some embodiments of the second aspect of the invention, an anglebetween the lateral side of the second prong and the longitudinal axisof the hollow needle is at least about 20 degrees. In some embodiments,the angle between the lateral side of the second prong and thelongitudinal axis of the hollow needle is between about 20 and about 40degrees. In some embodiments, the angle between the lateral side of thesecond prong and the longitudinal axis of the hollow needle is about 30degrees. In some embodiments of the second aspect of the invention, anangle between a lateral side of the second prong and a longitudinal axisof the hollow needle is less than about 20 degrees. In some embodiments,the angle between the lateral side of the second prong and thelongitudinal axis of the hollow needle is between about 5 degrees andabout 20 degrees.

In some embodiments of the first and second aspects of the invention,the first prong of the hollow needle includes a tip micro-feature. Insome embodiments, each of the first and second prongs of the hollowneedle includes a tip micro-feature. In some embodiments, the tipmicro-feature is a hole or a slit. In some embodiments, the slit is arectangular-shaped slit, a square-shaped slit, a U-shaped slit, or aT-shaped slit. In some embodiments, the tip micro-feature intersects theinner wall of the hollow needle at a non-perpendicular angle.

In some embodiments of the first and second aspects of the invention,the apparatus includes a plurality of hollow needles. In someembodiments, the distance between adjacent hollow needles is about 15 mmor less.

In some embodiments of the first and second aspects of the invention,the hollow needle is treated with a coating. In some embodiments, thecoating is selected from the group consisting of TiN, TiCN, TiAlN, ZrN,and a diamond-like carbon.

In some embodiments of the first and second aspects of the invention,the inner diameter of the hollow needle is between about 0.14 mm and0.84 mm. In some embodiments, the inner diameter of the hollow needle isbetween about 0.24 mm and 0.40 mm.

In some embodiments of the first and second aspects of the invention,the gauge size of the hollow needle is between 18 and 30 gauge. In someembodiments, the gauge size of the hollow needle is between 22 and 25gauge.

In some embodiments of the first and second aspects of the invention,the length of the hollow needle is between about 2 mm and about 5 mm.

In some embodiments of the first and second aspects of the invention,the hollow needle is configured to extend (i) into the dermal layer,(ii) through the entire dermal layer to the junction of the dermal layerand the subcutaneous fat layer, or (iii) into the subcutaneous fatlayer.

In some embodiments of the first and second aspects of the invention,the apparatus is configured to remove an areal fraction of the skintissue that is between about 0.01 to about 0.65. In some embodiments,the apparatus is configured to remove an areal fraction of the skintissue that is between about 0.01 to about 0.05. In some embodiments,the apparatus is configured to remove an areal fraction of the skintissue that is between about 0.02 to about 0.03 (e.g., about 0.025).

In some embodiments of the first and second aspects of the invention,the inner wall of the hollow needle has a surface roughness betweenabout 150 and about 300 Rz.

In some embodiments of the first and second aspects of the invention,the hollow needle includes a lumen, wherein the apparatus furtherincludes a tissue removal tool within the lumen of the hollow needle andwherein the tissue removal tool is configured to facilitate removal ofportions of the skin tissue from the hollow needle. In some embodiments,the tissue removal tool is controllably translatable along thelongitudinal axis of the hollow needle. In some embodiments, the tissueremoval tool is a piston. In some embodiments, the piston includes around tip at a distal end of the piston. In some embodiments, theportions of the skin tissue removed by the tissue removal tool from thelumen of the hollow needle are substantially intact tissue portions.

In some embodiments of the first and second aspects of the invention,the apparatus further includes an aspiration tube, wherein theaspiration tube is coupled to a low pressure source and a trap. In someembodiments, the aspiration tube is placed in close proximity to thedistal end of the hollow needle and wherein the trap is configured tocapture the portions of the skin tissue to be discarded. In someembodiments, the low pressure source is a vacuum pump.

In some embodiments of the first and second aspects of the invention,the apparatus further includes a low-pressure conduit coupled to thehollow needle, wherein the low-pressure conduit is connected to a lowpressure source to generate suction in the hollow needle. In someembodiments, the low pressure source is a vacuum pump.

In some embodiments of the first and second aspects of the invention,the apparatus further includes at least one actuator. In someembodiments, the actuator: 1) is configured to displace the hollowneedle back and forth along a direction substantially parallel to theaxis of the hollow needle; and/or 2) is configured to translate thehollow needle over the skin tissue in one direction or two orthogonaldirections. In some embodiments, the actuator is configured to displacethe hollow needle back and forth along a direction substantiallyparallel to the axis of the hollow needle and to translate the hollowneedle over the skin tissue in one direction or two orthogonaldirections. In some embodiments, the actuator is coupled to theapparatus by a locking or connecting mechanism. In some embodiments, thelocking or connecting mechanism is selected from the group consisting ofa magnetic latch, a compression clamp, a sliding clamp, a rotating lock,a clasp latch, and a sliding-rotating lock.

In some embodiments of the first and second aspects of the invention,the apparatus further includes a cover. In some embodiments, the coveris coupled to the actuator by a locking or connecting mechanism. In someembodiments, the locking or connecting mechanism is selected from thegroup consisting of a magnetic latch, a compression clamp, a slidingclamp, a rotating lock, a clasp latch, and a sliding-rotating lock.

In some embodiments of the first and second aspects of the invention,the apparatus further includes a spacer. In some embodiments, the spaceris attached to the cover, positioned between the cover and the skintissue, and/or configured to control the depth of insertion of thehollow needle.

In some embodiments of the first and second aspects of the invention,the apparatus is configured to produce an array pattern upon removal ofthe portions of the skin tissue. In some embodiments, the array patternincludes one or more rows or a semi-random spatial distribution.

In some embodiments of the first and second aspects of the invention,the hollow needle is repeatedly inserted into and withdrawn from theskin tissue.

In some embodiments of the first and second aspects of the invention,the first and/or second prong as described herein is resistant tocurling.

In a third aspect, the invention features a method for producing acosmetic effect in a skin tissue. The method includes producing aplurality of holes in the skin tissue using an apparatus describedherein, wherein each hole is produced by removing a portion of the skintissue.

In some embodiments of the third aspect of the invention, the diameterof each hole is between about 0.14 mm and 0.84 mm. In some embodiments,the diameter of each hole is between about 0.24 mm and 0.40 mm.

In some embodiments of the third aspect of the invention, a surface areafraction of the removed portions of the skin tissue is between about0.01 to about 0.65. In some embodiments, the surface area fraction ofthe removed portions of the skin tissue is less than about 0.1, such asbetween about 0.01 to about 0.05. In some embodiments, the surface areafraction of the removed portions of the skin tissue is between about0.02 to about 0.03 (e.g., 0.025).

In some embodiments of the third aspect of the invention, at least oneof the holes extends (i) into the dermal layer, (ii) through the entiredermal layer to the junction of the dermal layer and the subcutaneousfat layer, or (iii) into the subcutaneous fat layer. In someembodiments, at least one of the holes extends to a depth of betweenabout 2 mm and about 5 mm.

In some embodiments of the third aspect of the invention, an arraypattern including one or more rows or a semi-random spatial distributionis generated by the plurality of holes.

In a fourth aspect, the invention provides a hollow needle including atleast a first prong provided at a distal end of the hollow needle,wherein an angle (a) between a lateral side of the first prong and alongitudinal axis of the hollow needle is at least about 20 degrees, andwherein the hollow needle is configured to remove a portion of skintissue when the hollow needle is inserted into and withdrawn from skintissue.

In some embodiments of the fourth aspect of the invention, the angle (a)between the lateral side of the first prong and the longitudinal axis ofthe hollow needle is between about 20 and about 40 degrees. In someembodiments, the angle (a) between the lateral side of the first prongand the longitudinal axis of the hollow needle is about 30 degrees.

In some embodiments of the fourth aspect of the invention, the hollowneedle further includes a second prong. In some embodiments, an angle(a) between a lateral side of the second prong and a longitudinal axisof the hollow needle is at least about 20 degrees. In some embodiments,the angle (a) between the lateral side of the second prong and thelongitudinal axis of the hollow needle is between about 20 and about 40degrees. In some embodiments, the angle (a) between the lateral side ofthe second prong and the longitudinal axis of the hollow needle is about30 degrees. In some embodiments of the fourth aspect of the invention,an angle (a) between a lateral side of the second prong and alongitudinal axis of the hollow needle is less than about 20 degrees. Insome embodiments, the angle (a) between the lateral side of the secondprong and the longitudinal axis of the hollow needle is between about 5degrees and about 20 degrees.

In some embodiments of the fourth aspect of the invention, the firstprong includes an edge. In some embodiments, each of the first andsecond prongs includes an edge.

In some embodiments of the fourth aspect of the invention, the firstprong includes a flat tip. In some embodiments, each of the first andsecond prongs includes a flat tip. In some embodiments, the flat tip hasa length and a width. In some embodiments, the length and/or the widthis at an angle relative to the longitudinal axis of the hollow needle.In some embodiments, the length and/or the width is perpendicular to thelongitudinal axis of the hollow needle.

In a fifth aspect, the invention provides a hollow needle including atleast a first prong provided at a distal end of the hollow needle,wherein the first prong includes a flat tip having at least twodimensions, and wherein the hollow needle is configured to remove aportion of skin tissue when the hollow needle is inserted into andwithdrawn from skin tissue.

In some embodiments of the fifth aspect of the invention, the hollowneedle further includes a second prong. In some embodiments, the secondprong includes a flat tip. In some embodiments, the flat tip has alength and a width. In some embodiments, the length and/or the width isat an angle relative to the longitudinal axis of the hollow needle. Insome embodiments, the length and/or the width is perpendicular to thelongitudinal axis of the hollow needle.

In some embodiments of the fifth aspect of the invention, an angle (α)between a lateral side of the first prong and a longitudinal axis of thehollow needle is at least about 20 degrees. In some embodiments, theangle (α) between the lateral side of the first prong and thelongitudinal axis of the hollow needle is between about 20 and about 40degrees. In some embodiments, the angle (α) between the lateral side ofthe first prong and the longitudinal axis of the hollow needle is about30 degrees. In some embodiments of the fifth aspect of the invention, anangle (α) between a lateral side of the first prong and a longitudinalaxis of the hollow needle is less than about 20 degrees. In someembodiments, the angle (α) between the lateral side of the first prongand the longitudinal axis of the hollow needle is between about 5degrees and about 20 degrees.

In some embodiments of the fifth aspect of the invention, an angle (α)between a lateral side of the second prong and a longitudinal axis ofthe hollow needle is at least about 20 degrees. In some embodiments, theangle (α) between the lateral side of the second prong and thelongitudinal axis of the hollow needle is between about 20 and about 40degrees. In some embodiments, the angle (α) between the lateral side ofthe second prong and the longitudinal axis of the hollow needle is about30 degrees. In some embodiments of the fifth aspect of the invention, anangle (α) between a lateral side of the second prong and a longitudinalaxis of the hollow needle is less than about 20 degrees. In someembodiments, the angle (α) between the lateral side of the second prongand the longitudinal axis of the hollow needle is between about 5degrees and about 20 degrees.

In some embodiments of the fifth aspect of the invention, the firstprong of the hollow needle includes a tip micro-feature. In someembodiments, each of the first and second prongs of the hollow needleincludes a tip micro-feature. In some embodiments, the tip micro-featureis a hole or a slit. In some embodiments, the slit is arectangular-shaped slit, a square-shaped slit, a U-shaped slit, or aT-shaped slit. In some embodiments, the tip micro-feature intersects theinner wall of the hollow needle at a non-perpendicular angle.

In some embodiments of the fourth and fifth aspects of the invention,the hollow needle is treated with a coating. In some embodiments, thecoating is selected from the group consisting of TiN, TiCN, TiAlN, ZrN,and a diamond-like carbon.

In some embodiments of the fourth and fifth aspects of the invention,the hollow needle is repeatedly inserted into and withdrawn from theskin tissue.

In a sixth aspect, the invention features a needle assembly including ahollow needle, a z-actuator, and a tissue removal tool, wherein thehollow needle includes at least a first prong provided at a distal endof the hollow needle and wherein an angle (α) between a lateral side ofthe first prong and a longitudinal axis of the hollow needle is at leastabout 20 degrees.

In some embodiments of the sixth aspect of the invention, the hollowneedle further includes a second prong. In some embodiments, an angle(α) between a lateral side of the second prong and a longitudinal axisof the hollow needle is at least about 20 degrees. In some embodiments,an angle (α) between a lateral side of the second prong and alongitudinal axis of the hollow needle is less than about 20 degrees.

In some embodiments of the sixth aspect, the first prong includes anedge. In some embodiments, each of the first and second prongs includesan edge. In some embodiments, the first prong includes a flat tip. Insome embodiments, each of the first and second prongs includes a flattip. In some embodiments, the flat tip has a length and a width. In someembodiments, the length and/or the width is at an angle relative to thelongitudinal axis of the hollow needle. In some embodiments, the lengthand/or the width is perpendicular to the longitudinal axis of the hollowneedle.

In some embodiments, the needle assembly of the sixth aspect of theinvention further includes a support base, a scaffold, an aspirationtube, a trap, and/or a pressure generating source. In some embodiments,the needle assembly is configured to be detachably attached to an x-and/or y-actuator.

In a seventh aspect, the invention features a needle assembly includinga hollow needle, a z-actuator, and a tissue removal tool, wherein thehollow needle includes at least a first prong provided at a distal endof the hollow needle and wherein the first prong includes a flat tiphaving at least two dimensions.

In some embodiments of the seventh aspect, the hollow needle furtherincludes a second prong. In some embodiments, the second prong includesa flat tip. In some embodiments, the flat tip has a length and a width.In some embodiments, the length and/or the width is at an angle relativeto the longitudinal axis of the hollow needle. In some embodiments, thelength and/or the width is perpendicular to the longitudinal axis of thehollow needle.

In some embodiments of the seventh aspect, an angle (α) between alateral side of the first prong and a longitudinal axis of the hollowneedle is at least about 20 degrees. In some embodiments, an angle (α)between a lateral side of the first prong and a longitudinal axis of thehollow needle is less than about 20 degrees. In some embodiments of theseventh aspect, an angle (α) between a lateral side of the second prongand a longitudinal axis of the hollow needle is at least about 20degrees. In some embodiments, an angle (α) between a lateral side of thesecond prong and a longitudinal axis of the hollow needle is less thanabout 20 degrees.

In some embodiments, the needle assembly of the seventh aspect of theinvention further includes a support base, a scaffold, an aspirationtube, a trap, and/or a pressure generating source. In some embodiments,the needle assembly is configured to be detachably attached to an x-and/or y-actuator.

Definitions

By “tissue portion” is meant that portion of skin and/or proximal tissuelayers (e.g., epidermal layer, dermal layer, and subcutaneous fat layer)that is removed (e.g., as a plug) by a hollow needle of the apparatus. Atissue portion may have particular dimensions, geometry, and othercharacteristics that correspond to the particular dimensions, geometry,and other characteristics of a hollow needle of the apparatus of theinvention.

By removal of a tissue portion that is “substantially intact” is meantthat the tissue portion that is removed from the lumen of a hollowneedle remains as an unbroken or whole tissue portion, i.e., the removedtissue portion has not been broken or separated into individual, smallerpieces or macerated.

By “about” is meant +/−10% of the recited value.

By “subject” is meant a mammal (e.g., a human or non-human mammal).

By “proximal” or “proximal end” is meant the end of the hollow needlethat is away from or opposite the needle tip, e.g., the end of hollowneedle 14 that is closer to z-actuator 12 and support base 11, as shownin FIGS. 1A-1F.

By “distal” or “distal end” is meant the end of the hollow needle thatis at or close to the needle tip (e.g., needle tip 18 of FIGS. 1A-1F).

By “coring rate” is meant the percentage of hollow needle actuationsthat result in cored tissue removal from the treatment area out of thetotal number of hollow needle actuations. The hollow needles of theinvention are designed to maximize coring rate and minimize hollowneedle actuations that do not result in cored tissue removal. A tissueportion detaches from the skin when the coring force exceeds the tissueresistance force. The tissue resistance force is determined by theconnection of the tissue portion to its surrounding tissue. For example,when the hollow needle is fully inserted through the dermal layer of theskin, the tissue resistance force is determined by the connectionbetween the tissue portion in the lumen of the needle and thesubcutaneous fat layer. The coring rate is determined by, e.g., thecoring force of the hollow needle, the friction between the lumen wallof the hollow needle and the tissue portion, and the tissue resistanceforce. The coring rate may also be affected by applying a pressuredifferential across the hollow needle. For example, a vacuum applied atthe proximal end of the hollow needle may aspirate the cored tissueportion from the hollow needle, thereby, increasing the coring rate.

By “coring force” is meant the force applied by the hollow needle of theapparatus to the cored tissue portion as the needle is being withdrawnfrom the skin. The coring force is determined by, e.g., the frictionbetween the lumen wall of the hollow needle and the cored tissue portionas the needle is being withdrawn from the skin and the position,geometry, and orientation of micro-features in the hollow needle.

By “insertion force” is meant the force generated by the hollow needleon the skin as it is inserted into the skin. The insertion force isinitially determined by the amount of force required to penetrate thetissue. Once the tissue is penetrated, the insertion force is determineby the friction between the needle walls (inner and outer) and thesurrounding tissue, as well as the force required to separate the tissueat the tip of the needle.

Other features and advantages of the invention will be apparent from thefollowing Detailed Description and the claims.

DESCRIPTION OF THE DRAWINGS

FIGS. 1A, 1B, and 1C are schematic illustrations showing threeperspective views of a needle assembly of the invention.

FIG. 1D is a schematic illustration showing a cross-sectional view of aneedle assembly of the invention.

FIGS. 1E and 1F are exploded views showing individual components of aneedle assembly of the invention.

FIG. 2 is a schematic illustration showing possible needle prongconfigurations for a hollow needle.

FIG. 3 is a schematic illustration showing a side view of a prong of ahollow needle. A bevel angle α of a prong refers to the angle betweenlateral side 31 of the prong and longitudinal axis 32 of the hollowneedle.

FIG. 4 shows photographs that compare needle heel degradations after2,000, 8,000, and 10,000 actuation cycles of hollow needles having abevel angle of 10 degrees, 20 degrees, or 30 degrees.

FIGS. 5A, 5B, and 5C are schematic illustrations showing a hollow needlewith two prongs each having a sharp point at the tip of the prong, ahollow needle with two prongs each having an edge at the tip of theprong, and a hollow needle with two prongs each having a flat tip,respectively.

FIG. 5D is a schematic illustration showing a swaged hollow needle withtwo prongs each having an edge at the tip of the prong.

FIG. 5E is a schematic illustration showing a cross-sectional view ofthe swaged hollow needle shown in FIG. 5D.

FIGS. 6A and 6B are photographs showing micro-features at the tips ofthe hollow needles. FIG. 6A is a photograph showing the micro-feature asan oval-shaped hole at the needle tip and FIG. 6B is a photographshowing the micro-feature as a rectangular-shaped slit at the needletip.

FIG. 6C is a schematic illustration showing a hollow needle having twoprongs and a U-shaped micro-feature at the needle tip.

FIG. 7 is a schematic illustration showing a micro-feature intersectingthe inner wall of a hollow needle at a non-perpendicular angle andaffecting the resistance force applied by the cored tissue portioninside the hollow needle.

FIGS. 8A, 8B, 8C, and 8D are photographs showing that hollow needlescoated with diamond-like carbon (DLC) did not display any sign of needleheel degradation after 10,000 actuation cycles, while non-coated hollowneedle showed needle heel degradation after 10,000 actuation cycles.FIG. 8A is a photograph of a DLC-coated needle before undergoing anyactuation cycles; FIG. 8B is a photograph of the DLC-coated needle afterundergoing 5,000 actuation cycles; FIG. 8C is a photograph of theDLC-coated needle after undergoing 10,000 actuation cycles; and FIG. 8Dis a photograph of a non-coated needle after undergoing 10,000 actuationcycles.

FIG. 9 is a schematic illustration showing needle coring force andtissue resistance force on a cored tissue portion inside the lumen of ahollow needle.

FIG. 10 is a photograph of a round, polished end of a piston used toremove cored tissue portion(s) from the lumen of a hollow needle.

FIG. 11 is a schematic illustration showing an aspiration tube proximalto the tip of a hollow needle containing a cored tissue portion insideits lumen.

FIG. 12 is a photograph showing a cored tissue portion ejected from aneedle tip.

FIG. 13 is a schematic illustration showing a high pressure port used toaspirate a cored tissue portion from the proximal end of a hollow needleby applying a high pressure burst. The high pressure port is coupled toa tissue recovery port used to capture the aspirated cored tissueportion.

FIGS. 14A and 14B are schematic illustrations showing two differentspacers each coupled to the end of the cover of the apparatus. FIG. 14Ashows a “zero” spacer that allows a 10 mm extension of a hollow needleand FIG. 14B shows a “2 mm” spacer that allows an 8 mm extension of ahollow needle. The extension lengths shown are exemplary only and arenot meant to be limiting.

FIG. 15A is a photograph showing an actuation unit including x- andy-actuators.

FIG. 15B is a photograph showing a needle assembly of the inventionconnected to an actuation unit.

FIG. 16A is a photograph showing a cover used to enclose a needleassembly of the invention and an actuation unit.

FIGS. 16B and 16C are photographs showing a needle assembly of theinvention connected to an actuation unit before (FIG. 16B) and after(FIG. 16C) the needle assembly and the actuation unit are enclosed bythe cover shown in FIG. 16A.

FIGS. 16D, 16E, and 16F are schematic illustrations showing threeperspective views of an apparatus of the invention including a coverthat encloses a needle assembly and an actuation unit.

FIGS. 16G, 16H, and 16I are schematic illustrations showing threecross-sectional views of an apparatus of the invention including a coverthat encloses a needle assembly and an actuation unit.

FIGS. 16J, 16K, 16L, 16M, 16N, 16O, 16P, and 16Q are schematicillustrations showing eight views of the inside of an apparatus of theinvention including a needle assembly and an actuation unit.

FIGS. 16R, 16S, 16T, and 16U are exploded views showing four views ofthe inside of an apparatus of the invention including a needle assemblyand an actuation unit, which are detached.

FIGS. 17A, 17B, 17C, and 17D are schematic illustrations showing fourviews of a magnetic latch having parts 171 and 172.

FIGS. 17E and 17F are schematic illustrations showing twocross-sectional views of a magnetic latch having parts 171 and 172.

FIG. 17G is a schematic illustration showing part 171 of a magneticlatch.

FIGS. 17H and 17I are schematic illustrations showing part 172 of amagnetic latch.

FIGS. 18A, 18B, and 18C are schematic illustrations showing three viewsof a compression clamp having parts 181 and 182.

FIGS. 19A, 19B, and 19C are schematic illustrations showing three viewsof a sliding clamp having parts 191 and 192.

FIGS. 20A, 20B, and 20C are schematic illustrations showing three viewsof a rotating lock having parts 201 and 202.

FIGS. 20D and 20E are schematic illustrations showing twocross-sectional views of a rotating lock having parts 201 and 202.

FIGS. 21A, 21B, 21C, and 21D are schematic illustrations showing fourviews of a clasp latch having parts 211 and 212.

FIGS. 22A, 22B, 22C, and 22D are schematic illustrations showing fourviews of a sliding-rotating lock having parts 221 and 222.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to hollow needles, needle assemblies, actuationunits, apparatuses, kits, and methods for generating a cosmetic effectin the skin (e.g., eliminating tissue volume, tightening skin, and/orreducing skin laxity) by removing tissue portions from the skin. Withoutbeing bound by theory, this approach facilitates skin remodeling bydebulking the skin tissue and by triggering biological responses thatcontribute to tissue resurfacing and remodeling. In particular, theinvention relates to hollow needles, as well as related needleassemblies, apparatuses, kits, and methods, capable of coring tissueportions by capturing and retaining the tissue portions inside the lumenof the hollow needle after insertion into and withdrawal from the skin.The cored tissue portions can be removed from the lumen of the hollowneedle and discarded. The process can be repeated to generate multiplecored skin tissue portions, in particular over a desired area of skinand located at chosen sites of the body of a subject. The hollowneedles, needle assemblies, actuation units, apparatuses, kits, andmethods described herein provide increased effectiveness over currentlyavailable apparatuses and techniques while maintaining convenience,affordability, and accessibility to patients desiring tissuerestoration.

Needles

The apparatus of the invention includes at least one hollow needlehaving at least a first prong. In some embodiments, an angle between alateral side of the prong and a longitudinal axis of the hollow needle(e.g., a bevel angle α) is at least about 20 degrees (e.g., the bevelangle α may be greater than about 20 degrees, such as greater than 20degrees, 22 degrees, 24 degrees, 26 degrees, 28 degrees, 30 degrees, 32degrees, 34 degrees, 36 degrees, 38 degrees, and 40 degrees, or at anangle of about 20 to about 40 degrees, between 20 to 40 degrees, 20 to38 degrees, 20 to 36 degrees, 20 to 34 degrees, 20 to 32 degrees, 20 to30 degrees, 20 to 28 degrees, 20 to 26 degrees, 20 to 24 degrees, 20 to22 degrees, 22 to 40 degrees, 24 to 40 degrees, 26 to 40 degrees, 28 to40 degrees, 30 to 40 degrees, 32 to 40 degrees, 34 to 40 degrees, 36 to40 degrees, and 38 to 40 degrees). In particular, an angle between alateral side of the prong and a longitudinal axis of the hollow needle(e.g., a bevel angle α) is about 30 degrees.

In some embodiments, the tip of the prong of the hollow needle is anedge. In some embodiments, the tip of the prong of the hollow needle isa flat tip having at least two dimensions. In some embodiments, theprong of the hollow needle includes a tip micro-feature. The hollowneedles of the invention are constructed to prevent frequent needledamage during use, such as needle tip curling and wear (e.g., becomingdull), needle heel degradation, and needle bending. The hollow needlesof the invention are designed to maintain mechanical integrity anddurability over a large number of actuation cycles (e.g., actuationcycles greater than 1,000, 2,000, 3,000, 4,000, 5,000, 6,000, 7,000,8,000, 9,000, 1,0000, 11,000, 12,000, 13,000, 14,000, 15,000, or20,000). Preferably, these needles also effectively remove tissueportions from the skin with high coring rate. To produce a cosmeticeffect in the skin tissue, a hollow needle of the apparatus is insertedinto the skin tissue, preferably to a pre-determined depth using apre-determined force, such that the hollow needle removes a portion ofthe skin tissue by capturing the portion of the skin tissue in the lumenof the hollow needle.

Prongs

As shown in FIG. 2, distal end 20 of the hollow needle of the apparatus(e.g., the end of the needle that penetrates the skin tissue) can beshaped to form one or more prongs 21. The hollow needle of the apparatusmay have one prong at the distal end, two prongs, or more than twoprongs (e.g., three, four, five, or six prongs). A hollow needle havingone prong may be formed by grinding one side of the distal end of thehollow needle at an angle relative to the longitudinal axis of thehollow needle. A hollow needle having two prongs may be formed bygrinding opposite sides of the distal end of the hollow needle at anangle relative to the longitudinal axis of the hollow needle.

The geometry of a prong at the distal end of a hollow needle can becharacterized by a bevel angle. A bevel angle, e.g., angle α as shown inFIG. 3, refers to the angle between lateral side 31 of the prong andlongitudinal axis 32 of the hollow needle. An angle of “2α” refers tothe angle between two lateral sides of the prong of the hollow needle,e.g., the angle between lateral side 31 and lateral side 33 of thehollow needle. A bevel angle α between a lateral side of a prong and alongitudinal axis of the hollow needle may be at least about 20 degrees(e.g., between about 20 and about 40 degrees (e.g., 20, 22, 24, 26, 28,30, 32, 34, 36, 38, or 40 degrees)). In particular, an angle between alateral side of a prong and a longitudinal axis of the hollow needle maybe about 30 degrees. For hollow needles having two or more prongs (e.g.,FIG. 2), each prong may have the same bevel angle or different bevelangles. In one embodiment, for a hollow needle having two prongs, e.g.,a first prong and a second prong, an angle between a lateral side of thefirst prong and a longitudinal axis of the hollow needle may be betweenabout 20 and about 30 degrees (e.g., 20, 22, 24, 26, 28, or 30 degrees)and an angle between a lateral side of the second prong and alongitudinal axis of the hollow needle may be between about 30 and about40 degrees (e.g., 30, 32, 34, 36, 38, or 30 degrees). For example, thefirst prong may have a bevel angle α of 20 degrees and the second prongmay have a bevel angle α of 30 degrees.

A bevel angle α of at least about 20 degrees or more improves themechanical integrity of the needle over several actuation cycles ofinsertion and withdrawal into skin tissue. Table 1 below shows that atwo-prong hollow needle having a 2α bevel angle of 40 degrees (the bevelangle α of each prong is 20 degrees) reduces the occurrence of needletip curling relative to a two-prong hollow needle having a 2α bevelangle of 20 degrees (the bevel angle α of each prong is 10 degrees). Atotal of 5 two-prong hollow needles each having a bevel angle α of 10°and 5 two-prong hollow needles each having a bevel angle α of 20° weretested.

TABLE 1 Number of Number of Needles showing Tip Curling Actuation Cycles10° Bevel Angle α 20° Bevel Angle α  5,000 1 0 10,000 2 0 15,000 2 020,000 3 1Additionally, FIG. 4 shows that increasing the needle bevel angle α of aprong also reduces the occurrence of needle heel degradation over alarge number of actuation cycles. As show in FIG. 4, a hollow needlehaving a bevel angle α of 10 degrees displayed signs of needle heeldegradation (indicated by dashed circles) before 2,000 actuation cycles,while a hollow needle having a bevel angle α of 20 degrees and a hollowneedle having a bevel angle α of 30 degrees showed no apparent sign ofneedle heel degradation over 10,000 actuation cycles.

The tip of a prong of a hollow needle may be of varying geometries. Forexample, the tip of a prong may have a sharp point (e.g., sharp point 51as shown in FIG. 5A) or an edge (e.g., a one-dimensional edge) (e.g.,edge 52 as shown in FIG. 5B). For a prong having an edge at the tip,each of the bevel angles of the prong may be at least about 20 degrees(e.g., from about 20 to about 40 degrees (e.g., about 30 degrees)). Fora hollow needle having two or more prongs, e.g., two prongs, the prongsmay have different bevel angles (e.g., a bevel angle α of about 20degrees at the first prong and a bevel angle α of about 30 degrees atthe second prong). The tip of a prong may be a flat tip (e.g., a flattip having two dimensions) (e.g., flat tip 53 as shown in FIG. 5C). Forexample, a flat tip has a length and a width. The surface (length/width)of the flat tip of the prong may be at an angle relative to thelongitudinal axis of the hollow needle. For example, the surface of theflat tip may be perpendicular to the longitudinal axis of the hollowneedle (e.g., at a 90 degree angle relative to the longitudinal axis ofthe hollow needle) or the surface of the flat tip may be at a non-90degree angle relative to the longitudinal axis of the hollow needle(e.g., between about 3 to about 89 degrees, such as 3 to 89 degrees,e.g., 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51,54, 57, 60, 63, 66, 69, 72, 75, 78, 81, 84, 87, and 89 degrees). Thesurface of the flat tip may be level or may have different geometry,e.g., arc, groove, or non-level. For a prong having a two-dimensionalflat tip, each of the bevel angles of the prong may be between about 2degrees to about 40 degrees (e.g., 2, 4, 6, 8, 10, 12, 14, 16, 18, 20,22, 24, 26, 28, 30, 32, 34, 36, 38, or 40 degrees). The needle may haveone or two prongs each with a two-dimensional flat tip in which one orboth of the prongs have a bevel angle α of at least about 20 degrees(e.g., from about 20 to about 40 degrees (e.g., about 30 degrees)).Needles having a one-dimensional edge or a two-dimensional flat tipexhibit a reduced likelihood of needle tip curling.

Gauges, Inner Diameters, and Lengths

A hollow needle of the apparatus of the invention may be of any gauge,including gauges of from 18 to 30 (e.g., 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, and 30 gauge). The gauges of a hollow needle may be from22 to 25 (e.g., 22, 23, 24, and 25 gauge). A hollow needle of theapparatus may have an inner diameter of from about 0.14 mm to about 0.84mm (e.g., 0.14, 0.15, 0.16, 0.17, 0.18, 0.19, 0.2, 0.21, 0.22, 0.23,0.24, 0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 0.32, 0.33, 0.34, 0.35,0.36, 0.37, 0.38, 0.39, 0.4, 0.41, 0.42, 0.43, 0.44, 0.45, 0.46, 0.47,0.48, 0.49, 0.5, 0.51, 0.52, 0.53, 0.54, 0.55, 0.56, 0.57, 0.58, 0.59,0.6, 0.61, 0.62, 0.63, 0.64, 0.65, 0.66, 0.67, 0.68, 0.69, 0.7, 0.71,0.72, 0.73, 0.74, 0.75, 0.76, 0.77, 0.78, 0.79, 0.8, 0.81, 0.82, 0.83,and 0.84 mm). The inner diameter of a hollow needle refers to thediameter of the inner lumen of the hollow needle. The inner diameter ofa hollow needle may be from about 0.24 mm to about 0.40 mm (e.g., 0.24,0.25, 0.26, 0.27, 0.28, 0.29, 0.3, 0.31, 0.32, 0.33, 0.34, 0.35, 0.36,0.37, 0.38, 0.39, and 0.4 mm). Accordingly, the diameter of a portion ofskin tissue removed by a hollow needle of the apparatus (e.g., a coredtissue portion) generally corresponds to the inner diameter of thehollow needle.

In some embodiments, the outer and/or inner diameter of a hollow needlemay vary across its lengths, such that the diameter of one region of thehollow needle may be different from the outer and/or inner diameter ofanother region of the same needle. The change in a diameter across thehollow needle may or may not be continuous. The hollow needle may or maynot be entirely cylindrical. For example, one or more hollow needles maybe rectangular, serrated, scalloped, and/or irregular in one or moredimensions and along some or all of their lengths. In some embodiments,the inner lumen diameter may vary along the length of a hollow needle.The invention also features a swaged hollow needle having a bevel angleα of at least 20 degrees (e.g., between about 20 and about 40 degrees(e.g., 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, or 40 degrees)) and avariable inner lumen diameter over its length. FIGS. 5D and 5E showswaged hollow needle 54 having a smaller diameter near the distal end ofthe hollow needle (e.g., near the end of the needle that penetrates theskin tissue). FIG. 5D shows the outside of swaged hollow needle 54 andFIG. 5E shows a longitudinal cross-section of swaged hollow needle 54.In other embodiments, the inner diameter may be wider at the proximalend of a hollow needle (e.g., away from the tip that penetrates theskin). This may facilitate the removal of the cored tissue portion fromthe hollow needle, may limit the need for clearing of the hollow needle,and may reduce the occurrence of needle clogging.

A hollow needle of the apparatus may be of varying lengths and may havevarying active lengths (e.g., the length of a hollow needle configuredto penetrate the skin tissue). Active lengths may vary from about 0.5 mmto about 10 mm (e.g., 0.5, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8, 2, 2.2, 2.4,2.6, 2.8, 3, 3.2, 3.4, 3.6, 3.8, 4, 4.2, 4.4, 4.6, 4.8, 5, 5.2, 5.4,5.6, 5.8, 6, 6.2, 6.4, 6.6, 6.8, 7, 7.2, 7.4, 7.6, 7.8, 8, 8.2, 8.4,8.6, 8.8, 9, 9.2, 9.4, 9.6, 9.8, and 10 mm) and may be selectable withmanual or automatic controls (e.g., a scroll wheel or an actuationmechanism such as an electromagnetic actuator). Active lengths of ahollow needle may be adjusted and selected depending on the skin areaneeding treatment. For example, hollow needle with active lengths fromabout 0.5 mm to about 2 mm (e.g., 0.5, 0.6, 0.8, 1, 1.2, 1.4, 1.6, 1.8,and 2 mm) may be used to treat thin skin, e.g., skin of an eyelid. Thethickness of the epidermal and dermal layers of the skin of an eyelidmay be from about 0.5 mm to about 1 mm (e.g., 0.5, 0.6, 0.8, and 1).Hollow needles with active lengths from about 5 mm to about 10 mm (e.g.,5, 6, 7, 8, 9, and 10 mm) may be used to treat thick skin, e.g., skin ofthe back or scar tissue, which can be thicker than healthy skin tissue.The thickness of an epidermal layer of skin may be from about 0.05 toabout 2 mm (e.g., 0.05 to 2, 0.05 to 1.95, 0.05 to 1.9, 0.05 to 1.85,0.05 to 1.8, 0.05 to 1.75, 0.05 to 1.7, 0.05 to 1.65, 0.05 to 1.6, 0.05to 1.55, 0.05 to 1.5, 0.05 to 1.45, 0.05 to 1.4, 0.05 to 1.35, 0.05 to1.3, 0.05 to 1.25, 0.05 to 1.2, 0.05 to 1.15, 0.05 to 1.1, 0.05 to 1.05,0.05 to 1, 0.05 to 0.95, 0.05 to 0.9, 0.05 to 0.85, 0.05 to 0.8, 0.05 to0.75, 0.05 to 0.7, 0.05 to 0.65, 0.05 to 0.6, 0.05 to 0.55, 0.05 to 0.5,0.05 to 0.45, 0.05 to 0.4, 0.05 to 0.35, 0.05 to 0.3, 0.05 to 0.25, 0.05to 0.2, 0.05 to 0.15, 0.05 to 0.1, 0.1 to 2, 0.15 to 2, 0.2 to 2, 0.25to 2, 0.3 to 2, 0.35 to 2, 0.4 to 2, 0.45 to 2, 0.5 to 2, 0.55 to 2, 0.6to 2, 0.65 to 2, 0.7 to 2, 0.75 to 2, 0.8 to 2, 0.85 to 2, 0.9 to 2,0.95 to 2, 1 to 2, 1.05 to 2, 1.15 to 2, 1.2 to 2, 1.25 to 2, 1.3 to 2,1.35 to 2, 1.4 to 2, 1.45 to 2, 1.5 to 2, 1.55 to 2, 1.6 to 2, 1.65 to2, 1.7 to 2, 1.75 to 2, 1.8 to 2, 1.85 to 2, 1.9 to 2, and 1.95 to 2mm). The thickness of a dermal layer of skin may be from 2 to 8 mm(e.g., 2 to 8, 2 to 7.5, 2 to 7, 2 to 6.5, 2 to 6, 2 to 5.5, 2 to 5, 2to 4.5, 2 to 4, 2 to 3.5, 2 to 3, 2 to 2.5, 2.5 to 8, 3 to 8, 3.5 to 8,4 to 8, 4.5 to 8, 5 to 8, 5.5 to 8, 6 to 8, 6.5 to 8, 7 to 8, and 7.5 to8 mm). Active lengths of a hollow needle may be adjusted and selected topenetrate the epidermal and/or the dermal layer of skin.

Active lengths of a hollow needle may also be adjusted using one or morespacers (see FIG. 14), which are described in detail further herein.Hollow needle parameters may be selected based on the area of skin andthe condition to be treated. For example, treatment of thin, lax skin onthe cheeks may benefit from a hollow needle having an active length ofabout 2 mm and medium gauge (e.g., 25 gauge), while treatment of thickskin on the back or treatment of scar tissue may benefit from a hollowneedle having an active length closer to 5 mm and a thicker gauge (e.g.,22 gauge). A hollow needle of the apparatus may be configured to extendto varying depths of the skin tissue. The depth of penetration of ahollow needle may be determined by the active length (e.g., from about 2mm to about 5 mm) of the hollow needle. A hollow needle may beconfigured to extend (i) into the dermal layer, (ii) through the entiredermal layer to the junction of the dermal layer and the subcutaneousfat layer, and/or (iii) into the subcutaneous fat layer.

Micro-Features

A hollow needle of the apparatus may include one or more micro-features.A micro-feature is an element of the hollow needle that functions tohelp the hollow needle to capture or “grab” the tissue portion to beremoved. A micro-feature may increase the coring rate of the hollowneedle. A micro-feature may be located anywhere along the active lengthof the hollow needle. As shown in FIGS. 6A and 6B, micro-feature 61 or62 is located near the tip of the hollow needle (e.g., a tipmicro-feature). For example, a tip micro-feature may be located near thetip of prong 21 of the hollow needle. In some embodiments, the distancebetween the tip of a prong of the hollow needle and the start of amicro-feature is from about 100 μm to about 5 mm (e.g., from 100 μm to 5mm, 200 μm to 5 mm, 300 μm to 5 mm, 400 μm to 5 mm, 500 μm to 5 mm, 600μm to 5 mm, 700 μm to 5 mm, 800 μm to 5 mm, 900 μm to 5 mm, 1 mm to 5mm, 1.1 mm to 5 mm, 1.2 mm to 5 mm, 1.3 mm to 5 mm, 1.4 mm to 5 mm, 1.5mm to 5 mm, 1.6 mm to 5 mm, 1.7 mm to 5 mm, 1.8 mm to 5 mm, 1.9 mm to 5mm, 2 mm to 5 mm, 2.1 mm to 5 mm, 2.2 mm to 5 mm, 2.3 mm to 5 mm, 2.4 mmto 5 mm, 2.5 mm to 5 mm, 2.6 mm to 5 mm, 2.7 mm to 5 mm, 2.8 mm to 5 mm,2.9 mm to 5 mm, 3 mm to 5 mm, 3.1 mm to 5 mm, 3.2 mm to 5 mm, 3.3 mm to5 mm, 3.4 mm to 5 mm, 3.5 mm to 5 mm, 3.6 mm to 5 mm, 3.7 mm to 5 mm,3.8 mm to 5 mm, 3.9 mm to 5 mm, 4 mm to 5 mm, 4.1 mm to 5 mm, 4.2 mm to5 mm, 4.3 mm to 5 mm, 4.4 mm to 5 mm, 4.5 mm to 5 mm, 4.6 mm to 5 mm,4.7 mm to 5 mm, 4.8 mm to 5 mm, 4.9 mm to 5 mm, 100 μm to 4.9 mm, 100 μmto 4.8 mm, 100 μm to 4.7 mm, 100 μm to 4.6 mm, 100 μm to 4.5 mm, 100 μmto 4.4 mm, 100 μm to 4.3 mm, 100 μm to 4.2 mm, 100 μm to 4.1 mm, 100 μmto 4 mm, 100 μm to 3.9 mm, 100 μm to 3.8 mm, 100 μm to 3.7 mm, 100 μm to3.6 mm, 100 μm to 3.5 mm, 100 μm to 3.4 mm, 100 μm to 3.3 mm, 100 μm to3.2 mm, 100 μm to 3.1 mm, 100 μm to 3 mm, 100 μm to 2.9 mm, 100 μm to2.8 mm, 100 μm to 2.7 mm, 100 μm to 2.6 mm, 100 μm to 2.5 mm, 100 μm to2.4 mm, 100 μm to 2.3 mm, 100 μm to 2.2 mm, 100 μm to 2.1 mm, 100 μm to2 mm, 100 μm to 1.9 mm, 100 μm to 5 mm, 100 μm to 1.8 mm, 100 μm to 1.7mm, 100 μm to 1.6 mm, 100 μm to 1.5 mm, 100 μm to 1.4 mm, 100 μm to 1.3mm, 100 μm to 1.2 mm, 100 μm to 1.1 mm, 100 μm to 1 mm, 100 μm to 900μm, 100 μm to 800 μm, 100 μm to 700 μm, 100 μm to 600 μm, 100 μm to 500μm, 100 μm to 400 μm, 100 μm to 300 μm, and 100 μm to 200 μm).

Micro-features may be of varying geometries. A micro-feature may be ahole (see hole 61 of FIG. 6A) (e.g., a circular hole or an oval-shapedhole) or a slit (see slit 62 of FIG. 6B). A slit may be arectangular-shaped slit, a square-shaped slit, a U-shaped slit, or aT-shaped slit. The shape and dimensions of the micro-feature can beoptimized to maximize the ability of the hollow needle to capture aportion of the skin tissue, while minimizing the impact on themechanical robustness and integrity of the hollow needle. In someembodiments, a micro-feature may be a circular hole having a diameter offrom about 10 μm to about 1 mm (e.g., from 10 μm to 1 mm, 10 μm to 900μm, 10 μm to 880 μm, 10 μm to 860 μm, 10 μm to 840 μm, 10 μm to 820 μm,10 μm to 800 μm, 10 μm to 780 μm, 10 μm to 760 μm, 10 μm to 740 μm, 10μm to 720 μm, 10 μm to 700 μm, 10 μm to 680 μm, 10 μm to 660 μm, 10 μmto 640 μm, 10 μm to 620 μm, 10 μm to 600 μm, 10 μm to 580 μm, 10 μm to560 μm, 10 μm to 540 μm, 10 μm to 520 μm, 10 μm to 500 μm, 10 μm to 480μm, 10 μm to 460 μm, 10 μm to 440 μm, 10 μm to 420 μm, 10 μm to 400 μm,10 μm to 380 μm, 10 μm to 360 μm, 10 μm to 340 μm, 10 μm to 320 μm, 10μm to 300 μm, 10 μm to 280 μm, 10 μm to 260 μm, 10 μm to 240 μm, 10 μmto 220 μm, 10 μm to 200 μm, 10 μm to 180 μm, 10 μm to 160 μm, 10 μm to140 μm, 10 μm to 120 μm, 10 μm to 100 μm, 10 μm to 80 μm, 10 μm to 60μm, 10 μm to 40 μm, 10 μm to 20 μm, 20 μm to 1 mm, 40 μm to 1 mm, 60 μmto 1 mm, 80 μm to 1 mm, 100 μm to 1 mm, 120 μm to 1 mm, 140 μm to 1 mm,160 μm to 1 mm, 180 μm to 1 mm, 200 μm to 1 mm, 220 μm to 1 mm, 240 μmto 1 mm, 260 μm to 1 mm, 280 μm to 1 mm, 300 μm to 1 mm, 320 μm to 1 mm,340 μm to 1 mm, 360 μm to 1 mm, 380 μm to 1 mm, 400 μm to 1 mm, 420 μmto 1 mm, 440 μm to 1 mm, 460 μm to 1 mm, 480 μm to 1 mm, 500 μm to 1 mm,520 μm to 1 mm, 540 μm to 1 mm, 560 μm to 1 mm, 580 μm to 1 mm, 600 μmto 1 mm, 620 μm to 1 mm, 640 μm to 1 mm, 660 μm to 1 mm, 680 μm to 1 mm,700 μm to 1 mm, 720 μm to 1 mm, 740 μm to 1 mm, 760 μm to 1 mm, 780 μmto 1 mm, 800 μm to 1 mm, 820 μm to 1 mm, 840 μm to 1 mm, 860 μm to 1 mm,880 μm to 1 mm, 900 μm to 1 mm, 920 μm to 1 mm, 940 μm to 1 mm, 960 μmto 1 mm, and 980 μm to 1 mm).

In some embodiments, a micro-feature may be a slit having a length and awidth (e.g., a rectangular-shaped slit, a square-shaped slit, a U-shapedslit, or a T-shaped slit), in which the length or width may be fromabout 10 μm to about 1 mm (e.g., from 10 μm to 1 mm, 10 μm to 900 μm, 10μm to 880 μm, 10 μm to 860 μm, 10 μm to 840 μm, 10 μm to 820 μm, 10 μmto 800 μm, 10 μm to 780 μm, 10 μm to 760 μm, 10 μm to 740 μm, 10 μm to720 μm, 10 μm to 700 μm, 10 μm to 680 μm, 10 μm to 660 μm, 10 μm to 640μm, 10 μm to 620 μm, 10 μm to 600 μm, 10 μm to 580 μm, 10 μm to 560 μm,10 μm to 540 μm, 10 μm to 520 μm, 10 μm to 500 μm, 10 μm to 480 μm, 10μm to 460 μm, 10 μm to 440 μm, 10 μm to 420 μm, 10 μm to 400 μm, 10 μmto 380 μm, 10 μm to 360 μm, 10 μm to 340 μm, 10 μm to 320 μm, 10 μm to300 μm, 10 μm to 280 μm, 10 μm to 260 μm, 10 μm to 240 μm, 10 μm to 220μm, 10 μm to 200 μm, 10 μm to 180 μm, 10 μm to 160 μm, 10 μm to 140 μm,10 μm to 120 μm, 10 μm to 100 μm, 10 μm to 80 μm, 10 μm to 60 μm, 10 μmto 40 μm, 10 μm to 20 μm, 20 μm to 1 mm, 40 μm to 1 mm, 60 μm to 1 mm,80 μm to 1 mm, 100 μm to 1 mm, 120 μm to 1 mm, 140 μm to 1 mm, 160 μm to1 mm, 180 μm to 1 mm, 200 μm to 1 mm, 220 μm to 1 mm, 240 μm to 1 mm,260 μm to 1 mm, 280 μm to 1 mm, 300 μm to 1 mm, 320 μm to 1 mm, 340 μmto 1 mm, 360 μm to 1 mm, 380 μm to 1 mm, 400 μm to 1 mm, 420 μm to 1 mm,440 μm to 1 mm, 460 μm to 1 mm, 480 μm to 1 mm, 500 μm to 1 mm, 520 μmto 1 mm, 540 μm to 1 mm, 560 μm to 1 mm, 580 μm to 1 mm, 600 μm to 1 mm,620 μm to 1 mm, 640 μm to 1 mm, 660 μm to 1 mm, 680 μm to 1 mm, 700 μmto 1 mm, 720 μm to 1 mm, 740 μm to 1 mm, 760 μm to 1 mm, 780 μm to 1 mm,800 μm to 1 mm, 820 μm to 1 mm, 840 μm to 1 mm, 860 μm to 1 mm, 880 μmto 1 mm, 900 μm to 1 mm, 920 μm to 1 mm, 940 μm to 1 mm, 960 μm to 1 mm,and 980 μm to 1 mm).

The micro-features may be designed and constructed to have a directionaleffect on the tissue portion captured inside the lumen of the hollowneedle. For example, the shape and orientation of the micro-feature mayaffect the coring force of the hollow needle. As shown in FIG. 6C,U-shaped slit 63 creates a hook near tip 21 of the hollow needle, whichmay help to retain the tissue portion inside the lumen of the hollowneedle upon withdrawal of the needle from the skin. A micro-feature canintersect the inner wall of the hollow needle at a sharp edge, which candirectionally affect the coring force of the hollow needle, as well asthe resistance force applied by the cored tissue portion inside thelumen of the hollow needle. A micro-feature (e.g., a hole or a slit)drilled or micro-machined into a hollow needle may intersect the innerwall of the hollow needle at a perpendicular angle or at anon-perpendicular angle (e.g., an angle of from about 5 degrees to lessthan about 90 degrees, such as 5 to 85 degrees, 5 to 80 degrees, 5 to 75degrees, 5 to 70 degrees, 5 to 65 degrees, 5 to 60 degrees, 5 to 55degrees, 5 to 50 degrees, 5 to 45 degrees, 5 to 40 degrees, 5 to 35degrees, 5 to 30 degrees, 5 to 25 degrees, 5 to 20 degrees, 5 to 15degrees, 5 to 10 degrees, 10 to 85 degrees, 15 to 85 degrees, 20 to 85degrees, 25 to 85 degrees, 30 to 85 degrees, 35 to 85 degrees, 40 to 85degrees, 45 to 85 degrees, 50 to 85 degrees, 55 to 85 degrees, 60 to 85degrees, 65 to 85 degrees, 70 to 85 degrees, 75 to 85 degrees, and 80 to85 degrees). For example, FIG. 7 shows hollow needle 14 containing tipmicro-feature 71 that intersects inner wall 72 of hollow needle at anon-perpendicular angle γ and creates sharp edge 73. As tissue portion74 enters the hollow needle from needle tip 18, tissue portion 74 istraveling in the direction of lower resistance. As hollow needle 14 isbeing withdrawn from the skin tissue, as well as once the hollow needle14 is released from the skin tissue, micro-feature 71 helps to retaintissue portion 74 inside the lumen of hollow needle 14 and preventstissue portion 74 from being released from hollow needle 14. One or moremicro-features may be micro-machined into the hollow needle throughavailable processes and techniques, such as laser drilling and wireelectrostatic discharge machining (EDM).

Needle Coating

A hollow needle of the apparatus may be coated with a material (e.g., ahard material) that improves or maintains the mechanical integrity,durability, and reliability of the hollow needle. The coating materialmay help to prevent damage, abrasion, and wear and tear of the needletip and heel during repeated insertions into and withdrawals from skintissue. Examples of materials (e.g., a hard material) that may be usedto coat a hollow needle of the apparatus include, but are not limitedto, TiN, TiCN, TiAlN, ZrN, and diamond-like carbon (DLC). The hardmaterial may be applied as a coating to the outside surface of a hollowneedle, the inner surface (e.g., the surface of the inner lumen) of ahollow needle, or both surfaces. FIGS. 8A-8C show that a hollow needlecoated with DLC exhibited a reduction in needle heel and tip degradationover 10,000 actuation cycles of insertions and withdrawals into pigskin, while a non-coated hollow needle showed needle heel and tipdegradation (indicated by dashed circles) over 10,000 actuation cyclesof insertions and withdrawals into pig skin (FIG. 8D).

Surface of Needle Lumen

The lumen surface of a hollow needle may affect the coring force, coringrate, and insertion force of the hollow needle. In particular, thefriction between the lumen surface and a cored tissue portion maydetermine the coring force, coring rate, and insertion force. The hollowneedles described herein are designed to maximize coring rate andminimize hollow needle insertions that do not result in cored tissueremoval. A tissue portion detaches from the skin when the coring force(e.g., the force applied by the hollow needle of the apparatus to thecored tissue portion as the needle is being withdrawn from the skin)exceeds the tissue resistance force, which is determined by theconnection of the tissue portion to its surrounding tissue. For example,when the hollow needle is fully inserted through the dermal layer of theskin, the tissue resistance force is determined by the connectionbetween the tissue portion in the lumen of the needle and thesubcutaneous fat layer. Accordingly, when the coring force exceeds thetissue resistance force, the cored tissue portion is captured in thelumen of the hollow needle and removed from the skin (FIG. 9). A roughlumen surface increases the friction between the cored tissue portionand the lumen surface, which may result in increased insertion force,increased coring force, and increased coring rate. Lubrication of thelumen surface reduces the friction between the cored tissue portion andthe lumen surface, which may result in decreased insertion force,decreased coring force, and decreased coring rate. An overly rough anduneven lumen surface may lead to high occurrence of needle degradation(e.g., needle heel and tip degradations), may cause difficulty inremoving cored tissue portions from the lumen, and/or may cause needleclogging. The degree of roughness of the lumen surface may be optimizedto increase the coring force and coring rate without compromising thedurability of the needle, the insertion force, the ability to removetissue from the needle lumen, and the resistance of the needle todegradation (e.g., needle heel and tip degradation).

In some embodiments, hollow needles and methods of the invention mayhave a coring rate of at least about 5% (e.g., from about 5% to about100%, such as 5% to 100%, 5% to 95%, 5% to 90%, 5% to 85%, 5% to 80%, 5%to 75%, 5% to 70%, 5% to 65%, 5% to 60%, 5% to 55%, 5% to 50%, 5% to45%, 5% to 40%, 5% to 35%, 5% to 30%, 5% to 25%, 5% to 20%, 5% to 15%,5% to 10%, 10% to 95%, 15% to 95%, 20% to 95%, 25% to 95%, 30% to 95%,35% to 95%, 40% to 95%, 45% to 95%, 50% to 95%, 55% to 95%, 60% to 95%,65% to 95%, 70% to 95%, 75% to 95%, 80% to 95%, 85% to 95%, and 90% to95%).

In some embodiments, hollow needles and methods of the invention mayhave a coring force of about 3 N to about 10 N (e.g., 3, 3.5, 4, 4.5, 5,5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, and 10 N). In some embodiments, atwo-prong hollow needle having a bevel angle α of 20 degrees may have acoring force of about 3 N to about 10 N (e.g., 3, 3.5, 4, 4.5, 5, 5.5,6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, and 10 N).

A coating material and/or a lubricant may affect the degree of roughnessof the lumen surface, and thus the friction between the lumen surfaceand a cored tissue portion. The lumen surface of a hollow needle may bepolished by running a lubricant or a polishing media though the hollowneedle to reduce the roughness of the lumen surface. Examples oflubricants include, but are not limited to, salt-based lubricants (e.g.,buffered saline solutions (e.g., PBS)), sugar-based lubricants (e.g.,sucrose and glucose solutions), and surfactant-based lubricants (e.g.,solutions containing Tween20). The degree of roughness of the lumensurface of the hollow needle may also be affected by the manufacturingprocess used to make the hollow needle. Table 2 below shows lumensurface roughness measured in Ra (arithmetic average of roughnessprofile) and Rz (mean roughness depth) of hollow needles made usingsingle plug, double plug, and sunk manufacturing processes. The lumensurface of hollow needles made using double plug process is smoother(lower Ra and Rz values) than the lumen surface of hollow needles madeusing single plug process.

TABLE 2 Manufacturing Process Ra Rz Single plug 53 299 Double plug 37206 Sunk 56 330

Needle Manufacture

A hollow needle of the apparatus may be made using availablemanufacturing techniques and processes. For example, manufacturing of ahollow needle starts with drawing the needle hypodermic tube, followedby forming the needle tip. The needle hypodermic tube may be drawn usingmanufacturing processes, e.g., single plug, double plug, and sunk. Theneedle tip may be formed by grinding. For example, a hollow needlehaving one prong may be formed by grinding one side of the distal end ofthe hollow needle at an angle relative to the longitudinal axis of thehollow needle. Similarly, a hollow needle having two prongs may beformed by grinding opposite sides of the distal end of the hollow needleat an angle relative to the longitudinal axis of the hollow needle. Thegrinding process may be performed at a low temperature to prevent orreduce annealing of the needle material and to prevent the needlematerial from undergoing phase transitions at high temperatures (e.g.,at alloy transition temperature, which is defined by the alloystoichiometry). Annealed material may become ductile and more prone tobending, which may reduce the durability and mechanical integrity of thehollow needle. Maintaining a low temperature (e.g., a temperature lowerthan the alloy transition temperature) during the grinding process maybe achieved by, e.g., reducing the grinding speed and/or grinding rateand using a cooling fluid (e.g., periodically submerging the needlematerial and/or the grinding machinery in a cooling fluid). In someembodiments, the cooling fluid used may be at room temperature. Othernon-grinding techniques and processes may also be used to manufacturethe hollow needle(s) of the apparatus, e.g., electrical dischargemachining.

Needle Assembly

FIGS. 1A-1F are schematic illustrations of an exemplary needle assembly10 of the invention including support base 11, z-actuator (e.g., a voicecoil) 12, tissue removal tool (e.g., a piston) 13, hollow needle 14,aspiration tube 15, trap 16, pressure generating source (e.g., a vacuumpump) 17, and scaffold 18. Such a needle assembly may permit treatmentof multiple areas of a subject without forcing the subject to move, incontrast to other, larger medical treatment systems. A needle assemblyof the apparatus (e.g., needle assembly 10 shown in FIGS. 1A-1F, 15B,and 16G-16U) may be detachably attached to other components of theapparatus (e.g., to an actuation unit of the apparatus) for easy andquick connection and disconnection. In some embodiments, the needleassembly (e.g., needle assembly 10) may be detachably attached to anactuation unit of the apparatus (e.g., actuation unit 151 shown in FIGS.15A, 15B, 16B, and 16G-16U) using a locking or connecting mechanism(described further herein; see FIGS. 17A-17I, 18A-18C, 19A-19C, 20A-20E,21A-21D, and 22A-22D). The entire needle assembly and/or components ofthe needle assembly may be detached from other components of theapparatus (e.g., detached from the actuation unit) to be replaced orsterilized after use.

Needle assembly 10 may include additional components, such as tubingand/or cables to couple various components and device controlelectronics, a power supply (e.g., an alternator and/or batterycomponent), and/or a user interface. The components of the needleassembly may be detachably engaged for easy and quick connection anddisconnection. The components of the needle assembly may be readilycleaned, sterilized (e.g., by steam sterilization or other knownmethods), and/or replaced. The components of the needle assembly may beprovided to an operator (e.g., a doctor or surgeon) in sterile conditionprior to use on a patient and many, if not all, of the components can bere-sterilized or replaced with sterile components prior to a subsequentuse. For example, components of the needle assembly and/or the entireneedle assembly may be readily removable from the apparatus forsterilization or replacement after use of the apparatus.

Z-actuator (e.g., a voice coil) 12 is configured to couple with hollowneedle 14 in needle assembly 10. Z-actuator (e.g., a voice coil) 12 mayhave a locking mechanism to secure the hollow needle 14 in place duringoperation. In some embodiments, z-actuator 12 and hollow needle 14 maybe locked by establishing a magnetic connection between the two. Inother embodiments, z-actuator 12 and hollow needle 14 may be locked byestablishing a mechanical connection between the two using, e.g.,quick-connect clasps. The z-actuator-hollow needle locking mechanism maybe detachably engaged for easy and quick connection and disconnection.The z-actuator-hollow needle locking mechanism may include one or moreof adhesive, magnetic, electrical, and/or mechanical components (e.g.,one or more gaskets, o-rings, septa, springs, clasps, and otherengagement members). In some embodiments, the z-actuator may include agroove or depression for placement of an o-ring (e.g., a viton o-ring, anitrile rubber o-ring, and a thermoplastic polyurethane o-ring) thatwill allow for a seal to form between z-actuator 12 and hollow needle14. The portion of hollow needle 14 engineered to engage with z-actuator12 may include a corresponding groove or depression. In otherembodiments, a locking mechanism may involve mated pieces made of moldedplastic. As an example, hollow needle 14 may form a seal by slidingpartway into z-actuator 12. Z-actuator 12 and hollow needle 14 may alsoinclude interlocking ridges (e.g., made of plastic, rubber, or othermaterial) to enhance or form a seal between the components. Z-actuator12 may also feature a mechanism to activate detachment of hollow needle14 from z-actuator 12. This mechanism may include one or more of abutton, key, switch, toggle, spin-wheel, touch screen, and/or slidinglock. The detachment mechanism may be a quick-release mechanism. In someembodiments, one component (e.g., z-actuator 12) includes a depressibleportion that engages a seal when the other component (e.g., hollowneedle 14) is slid into the other. Depression of the portion may bedisengaged by activation of a sliding lock, eliminating the seal betweenthe components to allow their separation and, e.g., removal andreplacement of hollow needle 14.

Needle assembly 10 may also include a power supply or be detachablyattached to a power supply. For example, needle assembly 10 may have aholder for batteries that power operation of the apparatus or may beconfigured to receive an element including batteries. The holder may beconfigured to charge the batteries (e.g., when depleted) with a pairedcharging station, without requiring removal of the batteries, or thebatteries may be removed from the apparatus for replacement or charging.In another embodiment, needle assembly 10 may include electronics andcomponents (e.g., a power cord) that allow it to be powered from anexternal power supply, such as a direct or alternating current supply ora generator.

Mechanisms for Removal of Cored Tissue Portion from Hollow Needle

Cored tissue portion(s) may require removal from the lumen of a hollowneedle of the apparatus after the needle containing the cored tissueportion inside its lumen is withdrawn from the skin, e.g., in order tocontinue the skin treatment procedure. The cored tissue portion may beremoved from the needle lumen after each actuation cycle or aftermultiple actuation cycles. In some embodiments, a tissue removal tool(e.g., a piston) may be inserted from the proximal end (e.g., the endopposite the needle tip) of the hollow needle to push out the coredtissue portion. In some embodiments, the cored tissue portion may beremoved through the distal end of the hollow needle (e.g., at the needletip) using an aspiration tube coupled to a pressure generating source(e.g., a vacuum). The cored tissue portion may also be removed throughthe proximal end of the hollow needle by applying a differentialpressure (e.g., a vacuum) or out of the distal end of the needle usingcompressed air or a pressurized fluid to push the cored tissue portionout of the distal end.

Tissue Removal Tool

A tissue removal tool may be used to push the cored tissue portion outof the lumen of a hollow needle. A tissue removal tool may be a pistonor a pin that can fit inside the lumen of the hollow needle (e.g.,without creating a vacuum inside the lumen (e.g., the gap between thetissue removal tool and the wall of the lumen of the hollow needle islarge enough to allow the passage of air)). In a preferred embodiment,the tissue removal tool is a piston. A tissue removal tool (e.g., apiston) does not disrupt the structural integrity of the cored tissueportion. In some embodiments, a tissue removal tool (e.g., a piston) maypush the cored tissue portion out of the lumen of a hollow needle as asubstantially intact, cored tissue portion (see, e.g., cored tissueportion 74 at needle tip 18 in FIG. 12), instead of as pieces of thecored tissue portion, which may be difficult to remove completely.Maintaining the structural integrity of the cored tissue portion as asubstantially intact tissue portion during the removal processfacilitates efficient and complete tissue removal from the hollowneedle.

A piston may be of varying geometry. The cross-section of the piston maybe, e.g., round, oval, rectangular, or square. In a preferredembodiment, the cross-section of the piston is round. The geometry ofthe piston matches the shape of the lumen of the hollow needle such thatthe piston fits well inside the lumen and is able to freely slide alongthe longitudinal axis of the hollow needle, for example, withoutcreating a vacuum. The piston may have a diameter that is less than theinner diameter of the hollow needle (e.g., a diameter that is 0.01% to10% less (e.g., 0.01%, 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%,0.4%, 0.45%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%,6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% less). The end of the piston,which touches the cored tissue portion as the piston pushes the coredtissue portion out of or towards the distal end of the needle, may beround or flat. For example, as shown in FIG. 10, end 101 of piston 102is round. A rounded piston end may prevent the attachment of the coredtissue portion to the piston during tissue removal. The piston may bepolished to minimize friction and abrasion between the piston and theinner wall of the hollow needle, thus reducing wear and tear of theinner wall.

The piston may stay at a constant position. In this example, the hollowneedle is moved up and down to engage the stationary piston. The pistonmay be inserted and withdrawn from the lumen of a hollow needle. Asshown in FIGS. 1A-1F, hollow needle 14 of needle assembly 10 moves downto penetrate into the skin and to capture and retain the cored tissueportion inside its lumen. As hollow needle 14 moves up to withdraw fromthe skin, it comes into contact with tissue removal tool (e.g., apiston) 13, which stays stationary. Tissue removal tool (e.g., a piston)13 is constructed to fit inside the lumen of the needle. Hollow needle14 continues to move upward, which allows tissue removal tool (e.g., apiston) 13 to extend further into the lumen and all the way to needletip 18, thereby pushing the cored tissue portion towards or out ofneedle tip 18.

In another example, after hollow needle 14 containing a cored tissueportion inside its lumen is withdrawn from the skin, tissue removal tool(e.g., a piston) 13 moves down towards to the end of hollow needle 14and enters the needle lumen through the proximal end of the needle. Inthis example, hollow needle 14 containing the cored tissue portion staysstationary while tissue removal tool (e.g., a piston) 13 moves downwardto needle tip 18, thereby pushing the cored tissue portion towards orout from needle tip 18. The length of tissue removal tool (e.g., apiston) 13 may be adjusted to allow the cored tissue portion to bepushed towards or out of needle tip 18 while the needle is in itsuppermost position and not penetrating into the skin. One or moreactuators (e.g., the x-, y-, and/or z-actuator) (e.g., actuation unit151 including x- and y-actuators shown in FIGS. 15A, 15B, and 16G-16U)may be coupled to a needle assembly (e.g., needle assembly 10 shown inFIGS. 1A-1F, 15B, and 16G-16U) to move the hollow needle (e.g., hollowneedle 14) away from the skin surface before the cored tissue portion ispushed out by the tissue removal tool (e.g., a piston; e.g., see tissueremoval tool 13 shown in FIGS. 1A-1F) such that the cored tissue portiondoes not drop onto the skin surface once it is pushed out.

An aspiration tube (e.g., aspiration tube 15 shown in FIGS. 1A-1F) maybe used in combination with a tissue removal tool (e.g., a piston) toremove the cored tissue portion from the needle tip. The aspiration tubemay stay at a constant position. As shown in FIG. 11, after cored tissueportion 74 is pushed to needle tip 18 by tissue removal tool (e.g., apiston), aspiration tube 15 located in proximity to needle tip 18 may beused to remove cored tissue portion 74 through a suction force. Theopening of aspiration tube 111 may be in proximity to needle tip 18 whenthe needle is in its uppermost position. Thus, once cored tissue portion74 is at needle tip 18, it can be aspirated into aspiration tube 15 byapplying suction using a pressure generating source (e.g., a vacuumpump).

As shown in FIGS. 1A-1F, pressure generating source (e.g., a vacuumpump) 17 may be connected to aspiration tube 15 to provide the suctionforce. In some embodiments, trap 16 may be installed between aspirationtube 15 and pressure generating source (e.g., a vacuum pump) 17 tocollect the cored tissue portions for disposal, subsequent use (e.g.,tissue graft or growth), or biochemical analysis and to prevent thecored tissue portion from entering pressure generating source (e.g., avacuum pump) 17. FIG. 12 further shows cored tissue portion 74 at needletip 18.

Differential Pressure

A cored tissue portion inside the lumen of a hollow needle may becollected at the proximal or distal end of the needle by applying adifferential pressure across the needle. In one embodiment, after theneedle containing the cored tissue portion inside its lumen is withdrawnfrom the skin, the needle may move to a dock station or a separate unit,which may contain a pressure generating source (e.g., a vacuum pump)that provides suction and/or vacuum at the proximal end of the needle.Suction and/or vacuum may be applied at the proximal end of the hollowneedle to pull the cored tissue portion out of the needle from itsproximal end. A trap may be installed at the proximal end of the needleand between the needle and the pressure generating source (e.g., avacuum pump) to collect the cored tissue portions for disposal,subsequent use (e.g., tissue graft or growth), or biochemical analysisand to prevent the cored tissue portions from entering the pressuregenerating source (e.g., a vacuum pump). In some embodiments, adifferential pressure may be applied to a hollow needle (e.g., a swagedhollow needle having a variable inner lumen diameter over its length anda bevel angle α of at least 20 degrees (e.g., swaged hollow needle 54)).Tissue removal may be facilitated by increasing the inner lumen diameterin the direction of the tissue removal. An increased inner lumendiameter in part of a hollow needle (e.g., a swaged hollow needle havinga variable inner lumen diameter over its length and a bevel angle α ofat least 20 degrees (e.g., swaged hollow needle 54)) may reduce thefriction between the cored tissue portion and the wall of the needlelumen. For example, suction and/or vacuum may be applied at the proximalend of a hollow needle (e.g., a swaged hollow needle having a variableinner lumen diameter over its length and a bevel angle α of at least 20degrees (e.g., swaged hollow needle 54)) to pull the cored tissueportion out from the proximal end.

In another arrangement, a burst of high pressure may be applied at theproximal end of a hollow needle to pull the cored tissue portion out ofthe needle from its proximal end. As illustrated in FIG. 13, highpressure port 131 may be coupled to tissue recovery port 132, whichcollects the cored tissue portions.

In another embodiment, after the needle containing the cored tissueportion inside its lumen is withdrawn from the skin, a pressuregenerating source (e.g., a vacuum pump) providing suction and/or vacuummay be placed proximal to the distal end of the needle. Suction and/orvacuum may be applied at the distal end of the hollow needle to pull thecored tissue portion out of the needle from its distal end.

In another embodiment, after the needle containing the cored tissueportion inside its lumen is withdrawn from the skin, a tissue removaltool (e.g., tissue removal tool (e.g., a piston) 13) may be used to pushthe cored tissue portion out of or towards the distal end of the needle.Once the cored tissue portion is at the distal end of the needle (e.g.,FIG. 12 showing cored tissue portion 74 at needle tip 18), suctionand/or vacuum may be applied at the distal end of the hollow needle toremove the cored tissue.

Non-limiting possible pressures for a pressure generating source (e.g.,a vacuum pump) to provide suction and/or vacuum at the proximal ordistal end of a hollow needle to remove a cored tissue portion from theneedle lumen include from about −8 mmHg to about −16 mmHg (e.g., −8, −9,−10, −11, −12, −13, −14, −15, and −16 mmHg). For example, the minimalair flow rate in the aspiration line of a pressure generating source(e.g., a vacuum pump) is from about 1 cubic feet per minute (CFM) toabout 6 CFM (e.g., 1, 2, 3, 4, 5, and 6 CFM (e.g., 3 CFM)).

Tissue Pressure

A cored tissue portion inside the lumen of a hollow needle may be pushedout of the proximal end of the needle by the insertion of one or morenew tissue portions during the subsequent actuation cycles. The innerwall of the hollow needle may be lubricated by, e.g., a sterile salinesolution, to prevent clogging of the needle as multiple tissue portionsare inserted into the needle. Also, a trap may be attached at theproximal end of the needle to collect the cored tissue portions as theyare being pushed out of the needle for disposal, subsequent use (e.g.,tissue graft or growth), or biochemical analysis.

Compressed Air or Pressurized Liquid

A cored tissue portion inside the lumen of the needle may be removedfrom the needle by applying compressed air or a pressurized fluid (e.g.,a sterile saline solution) through the needle. Compressed air orpressurized fluid may be applied through the proximal end to push thecored tissue portion out from the distal end of the needle.

Other Mechanisms for Removal of Cored Tissue Portion

A cored tissue portion inside the lumen of the needle may also beremoved from the needle using a heating element coupled to the needle.For example, a heating element coupled to the needle may be actuatedwhich causes the needle to heat up to facilitate separation of the coredtissue portion from the surrounding skin. The cored tissue portion maybe dried or desiccated prior to being removed from the lumen of thehollow needle. A vacuum source may then be applied to remove the heatedcored tissue portion.

Pressure Generating Source

The apparatus may further include or be otherwise coupled to a pressuregenerating source. A pressure generating source may be applied to removeand/or collect cored tissue portions from the lumen of a hollow needleto prevent needle clogging during operation. In one embodiment, suctionand/or vacuum may be applied via a hollow needle of the apparatus. Ahollow needle and a pressure generating source (e.g., a vacuum pump) maybe configured to remove and/or collect cored tissue portions from thelumen of the hollow needle by providing suction and/or vacuum afterpenetration of the hollow needle into the skin but before removal of thehollow needle from the skin. Following penetration into the tissue by ahollow needle, vacuum may be applied to draw the tissue portion in thelumen of the hollow needle from a treated skin area through the proximalend of the hollow needle and through tubing coupling the hollow needleto the pressure generating source (e.g., a vacuum pump). A trap may beinstalled between the proximal end of the hollow needle and the pressuregenerating source (e.g., a vacuum pump) to prevent the tissue portionfrom entering the pressure generating source (e.g., a vacuum pump). Thepressure generating source (e.g., a vacuum pump) may also be activatedafter the hollow needle containing the tissue portion in the lumen isremoved from the skin.

Alternatively, the pressure generating source (e.g., a vacuum pump) maybe integrated with a separate aspiration tube. For example, as describedpreviously and shown in FIGS. 1A-1F, tissue removal tool (e.g., apiston) 15 coupled to hollow needle 14 may slide freely from theproximal end to the distal end of the hollow needle to push the coredtissue portion towards or out of needle tip 18. Aspiration tube 15integrated with pressure generating source (e.g., a vacuum pump) 17 maybe placed proximal to needle tip 18 to provide suction and/or vacuumafter the cored tissue portion is pushed to needle tip 18. Trap 16 maybe installed between aspiration tube 15 and pressure generating source(e.g., a vacuum pump) 17 to prevent the cored tissue portion fromentering pressure generating source (e.g., vacuum pump) 17.

The pressure generating source may be a low pressure generating source.For example, the pressure generating source may be capable of providingvacuum and/or suction. Vacuum sources may include one or more rotarypumps, momentum transfer pumps, diffusion pumps, scroll pumps, and/ordiaphragm pumps. In some embodiments, a low pressure generating sourcemay include a house or central vacuum system. In other embodiments, asuction source may include a wall or portable suction device. In someembodiments, a vacuum source provides an absolute pressure less thanabout 6.3 kPa (e.g., from about 0.1 kPa to about 6 kPa, such as from 0.1kPa to 6 kPa, 0.1 kPa to 5 kPa, 0.1 kPa to 4 kPa, 0.1 kPa to 3 kPa, 0.1kPa to 2 kPa, 0.1 kPa to 1 kPa, 0.5 kPa to 6 kPa, 0.5 kPa to 5 kPa, 0.5kPa to 4 kPa, 0.5 kPa to 3 kPa, 0.5 kPa to 2 kPa, 0.5 kPa to 1 kPa, 1kPa to 6 kPa, 1 kPa to 5 kPa, 1 kPa to 4 kPa, 1 kPa to 3 kPa, 1 kPa to 2kPa, 1.5 kPa to 6 kPa, 1.5 kPa to 5 kPa, 1.5 kPa to 4 kPa, 1.5 kPa to 3kPa, and 1.5 kPa to 2 kPa).

Spacer

An apparatus of the invention may include one or more spacers thatfunction to control the depth of penetration of a hollow needle. Skinthickness varies significantly between body sites and in some cases,between subjects. Tissue penetration depth is important to ensure coringtissue portions of the appropriate size and to avoid injury to tissuelayers beyond the subcutaneous fat layer (e.g., muscle layer). One ormore spacers may be attached to the apparatus, e.g., between the coverof the apparatus and the skin (see FIGS. 14A, 14B, and 16A-16C). Aspacer is configured to control the depth of insertion of a hollowneedle and allows adjustments of the extension and penetration of thehollow needle into the skin. FIGS. 14A and 14B show two spacers 141 and142 that allow different insertion depths of hollow needle 14. Forexample, “zero” spacer 141 (FIG. 14A) attached to the distal end ofcover 161 of the apparatus allows a 10 mm insertion depth of hollowneedle 14. This type of spacer may be added to the distal end of thecover of the apparatus of the invention for coring thick skin tissues,which requires a deep penetration of the hollow needle. “2 mm” spacer142 (FIG. 14B) attached to the distal end of cover 161 of the apparatusallows an 8 mm insertion depth of hollow needle 14. Thick spacers (e.g.,spacer 142 of FIG. 14B) may be configured to decrease the depth ofpenetration of the hollow needle and may be used for coring thin skintissues, e.g., skin tissues of the face. Thin spacers (e.g., spacer 141of FIG. 14A) may be configured to increase the depth of penetration ofthe hollow needle and may be used for coring thick skin tissues.

Depending on the area of the skin tissue and/or the subject, spacers ofdifferent thicknesses may be placed at the distal end of the apparatus(e.g., on the end of a cover attached to the apparatus) to allowdifferent depths of tissue penetration. In some embodiments, a spacermay have a thickness of from about 0.01 mm to about 10 mm (e.g., from0.1 mm to 10 mm, 0.1 mm to 9.5 mm, 0.1 mm to 9 mm, 0.1 mm to 8.5 mm, 0.1mm to 8 mm, 0.1 mm to 7.5 mm, 0.1 mm to 7 mm, 0.1 mm to 6.5 mm, 0.1 mmto 6 mm, 0.1 mm to 5.5 mm, 0.1 mm to 5 mm, 0.1 mm to 4.5 mm, 0.1 mm to 4mm, 0.1 mm to 3.5 mm, 0.1 mm to 3 mm, 0.1 mm to 2.5 mm, 0.1 mm to 2 mm,0.1 mm to 1.5 mm, 0.1 mm to 1 mm, 0.1 mm to 0.5 mm, 0.1 mm to 10 mm, 0.5mm to 10 mm, 1 mm to 10 mm, 1.5 mm to 10 mm, 2 mm to 10 mm, 2.5 mm to 10mm, 3 mm to 10 mm, 3.5 mm to 10 mm, 4 mm to 10 mm, 4.5 mm to 10 mm, 5 mmto 10 mm, 5.5 mm to 10 mm, 6 mm to 10 mm, 6.5 mm to 10 mm, 7 mm to 10mm, 7.5 mm to 10 mm, 8 mm to 10 mm, 8.5 mm to 10 mm, 9 mm to 10 mm, and9.5 mm to 10 mm)

Actuation, Translation, and Position Detection Mechanisms

The apparatus may further include actuation mechanisms to drive a hollowneedle into or across the skin. In some embodiments, an actuation unitof the apparatus of the invention may include x-, y-, and z-actuators.Alternatively, an actuation unit of the apparatus of the invention(e.g., actuation unit 151 shown in FIGS. 15A and 15B) may include onlyx- and y-actuators, and a z-actuator (e.g., a voice coil) may be part ofthe needle assembly of the apparatus (e.g., z-actuator 12 of needleassembly 10 shown in FIGS. 1A-1F). In some embodiments, the “x,” “y,”and/or “z” actuators may drive a hollow needle into and/or across alarge area of skin surface in a relatively short amount of time comparedto manual deployment of a hollow needle. In other embodiments, the “x,”“y,” and/or “z” actuators may drive a hollow needle into and/or across asmall area of skin surface (e.g., a small area on the face (e.g., thearea between the nose and the upperlip)). In other embodiments, the “x,”“y,” and/or “z” actuators may drive a hollow needle into and/or acrossmultiple large and/or small areas of skin surface.

A “z” actuator may drive penetration into the skin by a hollow needleand/or retraction of the hollow needle after insertion. In someembodiments, a z-actuator (e.g., a voice coil) is part of the needleassembly of the apparatus (e.g., z-actuator 12 of needle assembly 10shown in FIGS. 1A-1F) and may be detachably attached to the needleassembly. The apparatus may include a feature or setting that has theability to control or change the depth of penetration of the hollowneedle into the skin. For example, a scroll wheel on a user interface ofthe base unit may adjust the allowed depth of penetration by the hollowneedle by physically retracting the hollow needle and/or providing anelectrical signal to a z-actuator. Alternatively, digital controls onthe user interface of the base unit may control the depth and/or timingof penetration into and retraction out of the skin by the hollow needle.For example, an operator may program a computer component of the baseunit to require a certain displacement of the hollow needle into theskin based upon the area being treated. The z-actuator may be programmedor otherwise set to displace the hollow needle up to about, e.g., 10 mminto thick skin (e.g., on a patient's back or into scar tissue), orabout, e.g., 1 mm into thin skin (e.g., on a patient's cheeks), forinstance. The z-actuator may be programmed or otherwise set to displacethe hollow needle to extend (i) into the dermal layer, (ii) through theentire dermal layer to the junction of the dermal layer and thesubcutaneous fat layer, or (iii) into the subcutaneous fat layer.

The z-actuator may also be capable of operating at a high speed tominimize treatment time and deflection of the skin during thepenetration of the hollow needle. In some embodiments, one actuationcycle in the z-direction takes from about 5 milliseconds to about 50milliseconds (e.g., 5, 10, 15, 20, 25, 30, 35, 40, 45, and 50milliseconds). In some embodiments, the z-actuator takes about 20 toabout 35 milliseconds (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, and 35 milliseconds) to travel about 20 mm to about 30mm (e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30 mm) downwardinto the skin tissue. In some embodiments, the z-actuator takes about 25milliseconds to about 30 milliseconds (e.g., 25, 26, 27, 28, 29, and 30milliseconds) to travel about 23 mm downward into the skin tissue. Insome embodiments, the z-actuator takes about 25 to about 35 milliseconds(e.g., 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, and 35 milliseconds(e.g., 30 milliseconds)) to travel about 20 mm to about 30 mm (e.g., 20,21, 22, 23, 24, 25, 26, 27, 28, 29, and 30 mm (e.g., 23 mm)) upward froma penetration depth of about 20 mm to about 30 mm (e.g., 20, 21, 22, 23,24, 25, 26, 27, 28, 29, and 30 mm (e.g., 23 mm)) into the skin tissue.In some embodiments, the z-actuator takes about 30 milliseconds totravel about 23 mm upward from the penetrated skin tissue.

The z-actuator may further be capable of operating with relatively highinsertion force. In some embodiments, a force of about 0.5 N to about 20N (e.g., 0.5 N to 0.75 N, 0.5 N to 1 N, 0.5 N to 1.25 N, 0.5 N to 1.5 N,0.5 N to 2 N, 0.5 N to 5 N, 0.5 N to 10 N, 0.5 N to 12 N, 0.5 N to 15 N,0.5 N to 20 N, 0.75 N to 1 N, 0.75 N to 1.25 N, 0.75 N to 1.5 N, 0.75 Nto 2 N, 0.75 N to 5 N, 0.75 N to 10 N, 0.75 N to 12 N, 0.75 N to 15 N,0.75 N to 20 N, 1 N to 1.25 N, 1 N to 1.5 N, 1 N to 2 N, 1 N to 5 N, 1 Nto 10 N, 1 N to 12 N, 1 N to 15 N, 1 N to 20 N, 1.25 N to 1.5 N, 1.25 Nto 2 N, 1.25 N to 5 N, 1.25 N to 10 N, 1.25 N to 12 N, 1.25 N to 15 N,1.25 N to 20 N, 1.5 N to 2 N, 1.5 N to 5 N, 1.5 N to 10 N, 1.5 N to 12N, 1.5 N to 15 N, 1.5 N to 20 N, 2 N to 5 N, 2 N to 10 N, 2 N to 12 N, 2N to 15 N, 2 N to 20 N, 5 N to 10 N, 5 N to 12 N, 5 N to 15 N, 5 N to 20N, 10 N to 12 N, 10 N to 15 N, 10 N to 20 N, 12 N to 15 N, 12 N to 20 N,and 15 N to 20 N) per hollow needle can be applied to ensure insertionof the hollow needle into the skin. In some embodiments, a force ofabout 10 N to 20 N (e.g., 15 N) per hollow needle can be applied toensure insertion of the hollow needle into the skin. The insertion forcemay be inversely correlated with needle gauge. For example, a 24 gaugeneedle may be operated with an insertion force of 12 N, while a 20 gaugeneedle may be operated with a higher insertion force. The z-actuator mayalso be capable of maintaining the apparatus at a low temperature (e.g.,less than about 43° C., such as less than about 43, 42, 41, 40, 39, 38,37, 36, or 35° C.) to avoid patient and user discomfort and/or to avoiddamage to the skin tissue (e.g., collagen in the skin tissue issensitive to high temperatures). Actuator types having thesecharacteristics include voice coil (VC) actuators, pneumatic actuators,electromagnetic actuators, motors with cams, motors with lead screws(e.g., stepper motors), and piezoelectric actuators. In someembodiments, the z-actuator is a VC actuator.

The apparatus may include an “x” and/or “y” actuator for translating ahollow needle across the skin. The x/y-actuator may be used to establishthe skin treatment coverage. In some embodiments, the x/y-actuator maybe characterized by a small displacement range (e.g., less than about 10mm (e.g., 10, 9, 8, 7, 6, 5, 4, 3, 2, and 1 mm)). In some embodiments,the x/y-actuator may be characterized by a relatively large displacementrange (e.g., up to about 30 mm). The x/y-actuator may operate with highpositional accuracy. For example, x/y-actuator may position the hollowneedle to penetrate the skin within a 30 μm radius (e.g., within 30, 25,20, 15, 10, or 5 μm) of a selected position. The x/y-actuator mayoperate with high position accuracy that allows continuous treatmentacross a treatment area. A treatment area may be a skin area thatcontains multiple treatment sites, e.g., a 3 cm by 3 cm treatment areacontaining nine 1 cm² treatment sites. The x/y-actuator may facilitatemovement of the hollow needle(s) of the apparatus from one treatmentsite to the adjacent treatment site within the treatment area. Thex/y-actuator may also facilitate movement of the hollow needle(s) of theapparatus within each treatment site. The x/y-actuator may operate withhigh position accuracy that avoid gaps between adjacent treatment sitesin the treatment area and/or avoid overlaps between adjacent treatmentsites in the treatment area.

The x/y-actuator may also operate at a relatively high speed to minimizetreatment time. In some embodiments, one actuation cycle in the x-and/or y-direction takes from about 50 milliseconds to about 250milliseconds (e.g., 50, 75, 100, 125, 150, 175, 200, 225, and 250milliseconds). In some embodiments, one actuation cycle in the x- and/ory-direction takes about 120 milliseconds to about 160 milliseconds(e.g., 120, 125, 130, 135, 140, 145, 150, 155, and 160 milliseconds(e.g., about 140 milliseconds)). In some embodiments, one actuationcycle in the x- and/or y-direction takes about 120 milliseconds to about160 milliseconds (e.g., 120, 125, 130, 135, 140, 145, 150, 155, and 160milliseconds (e.g., about 140 milliseconds)) to travel about 0.6 mm toabout 1 mm (e.g., 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, and 1 mm).In some embodiments, one actuation cycle in the x- and/or y-directiontakes about 140 milliseconds to travel about 0.833 mm.

In some embodiments, the x/y-actuator may be capable of operating with aforce of about 0.5 N to about 20 N (e.g., 0.5 N to 0.75 N, 0.5 N to 1 N,0.5 N to 1.25 N, 0.5 N to 1.5 N, 0.5 N to 2 N, 0.5 N to 5 N, 0.5 N to 10N, 0.5 N to 12 N, 0.5 N to 15 N, 0.5 N to 20 N, 0.75 N to 1 N, 0.75 N to1.25 N, 0.75 N to 1.5 N, 0.75 N to 2 N, 0.75 N to 5 N, 0.75 N to 10 N,0.75 N to 12 N, 0.75 N to 15 N, 0.75 N to 20 N, 1 N to 1.25 N, 1 N to1.5 N, 1 N to 2 N, 1 N to 5 N, 1 N to 10 N, 1 N to 12 N, 1 N to 15 N, 1N to 20 N, 1.25 N to 1.5 N, 1.25 N to 2 N, 1.25 N to 5 N, 1.25 N to 10N, 1.25 N to 12 N, 1.25 N to 15 N, 1.25 N to 20 N, 1.5 N to 2 N, 1.5 Nto 5 N, 1.5 N to 10 N, 1.5 N to 12 N, 1.5 N to 15 N, 1.5 N to 20 N, 2 Nto 5 N, 2 N to 10 N, 2 N to 12 N, 2 N to 15 N, 2 N to 20 N, N to 10 N, Nto 12 N, N to 15 N, N to 20 N, 10 N to 12 N, 10 N to 15 N, 10 N to 20 N,12 N to 15 N, 12 N to 20 N, and 15 N to 20 N) per hollow needle can beapplied to translate the needle across the skin. In some embodiments, aforce of about 5 N to 15 N (e.g., 10 N) per hollow needle can be appliedto translate the needle across the skin. The x/y-actuator may also becapable of operating at a low temperature (e.g., less than about 43° C.,such as less than about 43, 42, 41, 40, 39, 38, 37, 36, or 35° C.) inorder to avoid raising the apparatus temperature to a level that couldcause patient discomfort. Actuator types having these characteristicsinclude voice coil (VC) actuators, pneumatic actuators, electromagneticactuators, motors with cams, piezoelectric actuators, and motors withlead screws (e.g., stepper motors). In some embodiments, thex/y-actuator is a stepper motor with a lead screw.

In any of the apparatuses, one or more components of the apparatus maybe selected or designed to secure the one or more hollow needles and/orprevent or minimize angular movement (e.g., wobbling) of the hollowneedle(s). In some embodiments, the x-, y-, and/or z-actuator may becapable of operating without causing any significant angular movement(e.g., wobbling) of the hollow needle(s). In particular embodiments, thez-actuator may be capable of inserting and withdrawing the hollowneedle(s) in a linear fashion without any significant angular movement(e.g., wobbling) of the hollow needle(s). The hollow needle(s) may besecured to the needle assembly so as to minimize or reduce angularmovement of the needle(s) during insertion to less than 5 degrees, e.g.,less than 4, 3, or 2 degrees. An angular movement of the needle(s)during insertion of −1-1.5 degrees is within nominal tolerances, whereasan angular movement of the needle(s) during insertion of −4-5 degrees ormore is to be avoided, if possible. For example, components that joinhollow needle(s) to other components of the needle assembly may bedesigned with low mechanical tolerances to firmly secure the hollowneedle(s). This may reduce the prevalence of or lower the risk ofdestabilization and/or reduction in the structural integrity of hollowneedle(s) that may result from repeated use. For example, firmlysecuring the needle(s) may prevent and/or minimize dulling, bending, andcurling of needle tip(s) that could reduce the effectiveness of theneedle(s). Firmly securing the needle(s) may also reduce the risk ofover-striking (e.g., striking a hole produced by a needle more thanonce).

An actuation unit having an x-, y-, and/or z-actuator may be integratedinto the apparatus or may be detachably connected to the needle assemblyof the apparatus (e.g., needle assembly 10 show in FIGS. 1A-1F, 15B, and16G-16U). FIG. 15A shows actuation unit 151 including x- and y-actuatorsthat may be detachably attached to needle assembly 10 of the apparatus.FIG. 15B shows needle assembly 10 of the invention connected toactuation unit 151, which is covered in drape 152 to maintain sterilityand/or cleanness during the treatment process and to protect actuationunit 151, as well as the treatment area, from contamination. In someembodiments, the actuation unit (if external to the apparatus; actuationunit 151) may be connected to the support base of the needle assembly(e.g., support base 11 of needle assembly 10 shown in FIGS. 1A-1F). Insome embodiments, the actuation unit (e.g., actuation unit 151) and thesupport base (e.g., support base 11) may be connected by establishing avacuum connection. In other embodiments, the actuation unit (e.g.,actuation unit 151) and the support base (e.g., support base 11) may beconnected by establishing a magnetic connection. In other embodiments,the actuation unit (e.g., actuation unit 151) and the support base(e.g., support base 11) may be connected by establishing a mechanicalconnection using, e.g., quick-connect clasps. The actuation unit-supportbase connecting mechanism may be detachably engaged for easy and quickconnection and disconnection. The actuation unit-support base connectingmechanism may include one or more of adhesive, magnetic, electrical,and/or mechanical components (e.g., one or more gaskets, o-rings, septa,springs, clasps, and other engagement members). Various locking andconnecting mechanisms that may be used to couple an actuation unit(e.g., actuation unit 151) to a needle assembly of the apparatus (e.g.,to a support base of a needle assembly (e.g., support base 11 of needleassembly 10 shown in FIGS. 1A-1F)) are shown in FIGS. 17A-17I, 18A-18C,19A-19C, 20A-20E, 21A-21D, and 22A-22D and described in detail furtherherein.

In some embodiments, an actuation unit (e.g., actuation unit 151) and aneedle assembly of the invention (needle assembly 10 shown in FIGS.1A-1F, 16B, 16C, and 16G-16U) may be optionally enclosed in a cover,which may be used to keep the actuation unit and the needle assemblysterile. FIG. 16A shows an example of a cover, e.g., cover 161. Cover161 includes quick-connect clasps 162 that may be used to establish amechanical connection to the actuation unit (e.g., actuation unit 151)and the needle assembly of the invention (needle assembly 10 shown inFIGS. 1A-1F, 16B, 16C, and 16G-16U). FIGS. 16B and 16C show needleassembly 10 connected to actuation unit 151 before (FIG. 16A) and after(FIG. 16B) the needle assembly and the actuation unit are enclosed in bycover 161. Additionally, FIGS. 16D-16F show three views of apparatus 163including a cover (e.g., cover 161), which encloses a needle assembly(e.g., needle assembly 10) and an actuation unit (e.g., actuation unit151). FIGS. 16G-16I show cross-sectional views of the inside ofapparatus 163. FIGS. 16J-16Q show needle assembly 10 connected toactuation unit 151. FIGS. 16R-16U show disassembled needle assembly 10and actuation unit 151. Other connecting/sealing/enclosing options(e.g., a magnetic connection) are also available to engage a cover ofthe apparatus (e.g., cover 161).

The z-, x-, and y-actuators may be activated independently or togetherby one or more buttons, keys, toggles, switches, screws, dials, cursors,spin-wheels, or other components. In some embodiments, each of the z-,x-, and y-actuators can be separately controlled (e.g., using separateactivation components, such as a button, or by using separate controlsin a user interface).

The apparatus may further include a translation mechanism to drive theentire apparatus across the skin (e.g., x- and y-translation). Atranslation mechanism may include, e.g., driving wheels or rods. Atranslation mechanism may permit automatic or manual translation of theapparatus across the skin. Translating components (e.g., wheels) may bedisposed on the apparatus or be disposed external to the apparatus. Thetranslating mechanism may be activated by an activator, such as abutton, key, toggle, switch, screw, cursor, dial, spin-wheel, or othercomponent, and/or may be digitally controlled by a user interface.

The apparatus may also include a position detection mechanism, such asan optical tracking mechanism. A position detection mechanism (e.g., acamera, infrared sensor, photodiode, and LED and detector) may assist intracking movement of the apparatus in relation to a patient or atreatment area. The optical tracking mechanism may also facilitateplacement of the hollow needle on the skin surface in the instance ofmanual translation of the apparatus across the skin. Control electronicsfor a position detection mechanism may be disposed within the apparatusor external to the apparatus, e.g., in a base unit or separate computer.For example, the position detection mechanism may monitor the distancebetween the previous needle insertion and the current apparatus positionand send a signal to the control electronics to actuate the skinpenetration mechanism when the apparatus has reached the desiredposition (e.g., a position a defined distance from the position wherethe needles were last inserted). Desired distances and/or positions maybe controlled at user interface.

The apparatus may also include a guide or template to facilitate thepositioning of the hollow needle of the apparatus. A guide or templatemay contain one or more holes or openings that provide a pre-set arraypattern (described further herein) for the hollow needle of an apparatusof the invention to follow. The guide or template may be used alone orin combination with the position detection mechanism. The hollow needlemay be translated by the x- and/or y-actuators to move across the guideor template and follow the array pattern set by the guide or thetemplate to remove skin tissue portions at the holes or openings in theguide or template.

Locking or Connecting Mechanisms

A locking or connecting mechanism may be used to couple components andunits described herein, e.g., coupling of an actuation unit (e.g.,actuation unit 151) to a support base of the needle assembly (e.g.,support base 11) and coupling of an actuation unit (e.g., actuation unit151) to a cover of the apparatus (e.g., cover 161). A locking orconnecting mechanism may be established by a vacuum connection, amagnetic connection, and/or a mechanical connection (e.g., usingquick-connect clasps). A locking or connecting mechanism used to coupleadjacent components or units described herein may be detachably engagedfor easy and quick connection and disconnection. A locking or connectingmechanism may include one or more of adhesive, magnetic, electrical,and/or mechanical components (e.g., one or more gaskets, o-rings, septa,springs, clasps, and other engagement members).

Various locking or connecting mechanisms are shown in FIGS. 17A-17I,18A-18C, 19A-19C, 20A-20E, 21A-21D, and 22A-22D and described in detailfurther herein. FIGS. 17A-17D show four views of a magnetic latch havingparts 171 and 172. FIGS. 17A and 17B show disassembled parts 171 and 172of the magnetic latch; FIGS. 17C and 17D show assembled parts 171 and172 of the magnetic latch; FIGS. 17E and 17F show two cross-sectionalviews of the assembled magnetic latch; FIG. 17G shows the section ofpart 171 that is to be connected to part 172; and FIGS. 17H and 17I showtwo views of part 172 of the magnetic latch. FIGS. 18A-18C show threeviews of a compression clamp having parts 181 and 182. FIG. 18A showsdisassembled parts 181 and 182 of the compression clamp; FIG. 18B showsparts 181 and 182 assembled to form the compression clamp; and FIG. 18Cshows a cross-sectional view of the assembled compression clamp. FIGS.19A-19C show three views of a sliding clamp having parts 191 and 192.FIG. 19A shows disassembled parts 191 and 192 of the sliding clamp; FIG.19B shows parts 191 and 192 assembled to form the sliding clamp havingclamp-lock switch 193 in the unlocked position; and FIG. 19C shows parts191 and 192 assembled to form the sliding clamp having clamp-lock switch193 in the locked position. FIGS. 20A-20E show five views of a rotatinglock having parts 201 and 202. FIG. 20A shows disassembled parts 201 and202 of the rotating lock; FIG. 20B shows parts 201 and 202 assembled toform the rotating lock in the unlocked position; FIG. 20C shows parts201 and 202 assembled to form the rotating lock in the locked position;and FIGS. 20D and 20E show two cross-sectional views of the rotatinglock in the locked position. FIGS. 21A-21D shows four views of a clasplatch having parts 211 and 212. FIG. 21A shows parts 211 and 212assembled to form the clasp latch having lock clip 213 in the unlockedposition; FIGS. 21B and 21C show two views of parts 211 and 212assembled to form the clasp latch having lock clip 213 in the lockedposition; and FIG. 21D shows a cross-sectional view of the assembledclasp latch having lock clip 213 in the locked position. FIGS. 22A-22Dshow four views of a sliding-rotating lock having parts 221 and 222.FIG. 22A shows disassembled parts 221 and 222 of the sliding-rotatinglock; FIGS. 22B and 22C show parts 221 and 222 partly and fullyassembled to form the sliding-rotating lock having slide-lock switch 223in the unlocked position; and FIG. 22D shows parts 221 and 222 assembledto form the sliding-rotating lock having slide-lock switch 223 in thelocked position.

To use a locking or connecting mechanism shown in any one of FIGS.17A-17I, 18A-18C, 19A-19C, 20A-20E, 21A-21D, and 22A-22D to couple twoadjacent components or units, the first part of the locking orconnecting mechanism may be attached to one component or unit and thesecond part of the locking or connecting mechanism may be attached tothe adjacent component or unit. Alternatively, a component or unit ofthe apparatus may be functionalized as a part of the locking orconnecting mechanism. For example, an actuation unit (e.g., actuationunit 151) may be attached to part 171 shown in any one of FIGS. 17A-17Fand a support base of a needle assembly (e.g., support base 11 of needleassembly 10 shown in FIGS. 1A-1F) may be functionalized as part 172shown in any one of FIGS. 17A-17F. Accordingly, a magnetic latch may beformed to lock the actuation unit (e.g., actuation unit 151) with thesupport base of a needle assembly (e.g., support base 11).

Array Patterns

The one or more hollow needles of the apparatus may be configured toform an array pattern in the skin upon removal of the portions of theskin tissue. The array pattern may include holes in one or more rows orin a semi-random spatial distribution. The size and geometry of an arraypattern may be generated based on the area of skin and condition beingtreated. For example, a small array pattern may be generated fortreatment of the peri-oral area, while a large array pattern may besuitable for treatment of the abdomen. In some embodiments, an arraypattern may be generated using different numbers and/or arrangements ofa plurality of hollow needles. In some embodiments, an array pattern maybe generated using one hollow needle, which can undergo multipleactuation cycles and be translated across the surface of the skin regionby the x-actuator and/or y-actuator to generate the array pattern. Insome embodiments, an array pattern may be generated using a plurality ofhollow needles (e.g., an array of hollow needles), which can undergo oneor more actuation cycles to generate the array pattern. The number ofactuation cycles needed to generate an array pattern of holes in theskin tissue is determined by the size of the array pattern, the gauge orinner diameter of the hollow needle, the number of hollow needles, andthe amount of skin tissue to be removed, e.g., the areal fraction ofskin tissue removed. An “areal fraction” of tissue removed refers to thefraction of the skin tissue surface covered by the holes generated bythe hollow needle(s) of the apparatus. In other words, an areal fractionof tissue removed refers to the ratio of the area covered by the totalamount of cored tissue portions to the total skin treatment area. In oneembodiment, one or more hollow needles may be configured to remove anareal fraction of about 0.01 to about 0.65 (e.g., 0.01, 0.02, 0.03,0.04, 0.05, 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40, 0.45, 0.50, 0.55,0.60, and 0.65) of tissue within a treatment area. In anotherembodiment, one or more hollow needles may be configured to remove anareal fraction of less than about 0.1, such as about 0.01 to about 0.05(e.g., 0.01, 0.015, 0.02, 0.025, 0.03, 0.035, 0.04, 0.045, and 0.05) oftissue within a treatment area. In another embodiment, one or morehollow needles may be configured to remove an areal fraction of about0.02 to about 0.03 (e.g., 0.02, 0.021, 0.022, 0.023, 0.024, 0.025,0.026, 0.027, 0.028, 0.029, and 0.03, e.g., 0.025) of tissue within atreatment area. In some embodiments, an areal fraction of about 0.01 toabout 0.65 (e.g., 0.01, 0.02, 0.03, 0.04, 0.05, 0.10, 0.15, 0.20, 0.25,0.30, 0.35, 0.40, 0.45, 0.50, 0.55, 0.60, and 0.65) of tissue may beremoved within a treatment area for wrinkle reduction. In someembodiments, an areal fraction of about 0.02 to about 0.03 (e.g., 0.02,0.021, 0.022, 0.023, 0.024, 0.025, 0.026, 0.027, 0.028, 0.029, and 0.03,e.g., 0.025) of tissue may be removed within a treatment area forwrinkle reduction. Table 3 below shows the number of actuation cyclesrequired for the treatment of different body areas using a 24 gaugehollow needle.

TABLE 3 Total Treatment Areal Fraction Treatment Area of Tissue Numberof Site (cm²) Removed Actuation Cycles Cheek 120 0.1 15,782 Upper lip 100.1 1,315 Knee 120 0.1 15,782 Hand 100 0.1 13,151

The apparatus may be configured for detachable attachment to one or morehollow needles having the same or different configurations. Theapparatus may have as few as 1 or as many as hundreds of hollow needles.In some embodiments, 1-100 hollow needles may be present (e.g., 1-10,1-20, 1-30, 1-40, 1-50, 1-60, 1-70, 1-80, 1-90, 1-100, 3-10, 3-20, 3-30,3-40, 3-50, 3-60, 3-70, 3-80, 3-90, 3-100, 5-10, 5-20, 5-30, 5-40, 5-50,5-60, 5-70, 5-80, 5-90, 5-100, 10-20, 10-40, 10-60, 10-80, 10-100,20-40, 20-60, 20-80, 20-100, 40-60, 40-80, 40-100, 60-80, 60-100, or80-100 hollow needles). The use of an array of a plurality of hollowneedles to generate an array pattern may facilitate skin treatment overlarger areas and in less time.

The minimum distance between two hollow needles in an array of hollowneedles may be between about 0.1 mm to about 50 mm (e.g., from 0.1 mm to0.2 mm, 0.1 mm to 0.5 mm, 0.1 mm to 1 mm, 0.1 mm to 2 mm, 0.1 mm to 5mm, 0.1 mm to 10 mm, 0.1 mm to 15 mm, 0.1 mm to 20 mm, 0.1 mm to 30 mm,0.1 mm to 40 mm, 0.1 mm to 50 mm, 0.2 mm to 0.5 mm, 0.2 mm to 1 mm, 0.2mm to 2 mm, 0.2 mm to 5 mm, 0.2 mm to 10 mm, 0.2 mm to 15 mm, 0.2 mm to20 mm, 0.2 mm to 30 mm, 0.2 mm to 40 mm, 0.2 mm to 50 mm, 0.5 mm to 1mm, 0.5 mm to 2 mm, 0.5 mm to 5 mm, 0.5 mm to 10 mm, 0.5 mm to 15 mm,0.5 mm to 20 mm, 0.5 mm to 30 mm, 0.5 mm to 40 mm, 0.5 mm to 50 mm, 1 mmto 2 mm, 1 mm to 5 mm, 1 mm to 10 mm, 1 mm to 15 mm, 1 mm to 20 mm, 1 mmto 30 mm, 1 mm to 40 mm, 1 mm to 50 mm, 2 mm to 5 mm, 2 mm to 10 mm, 2mm to 15 mm, 2 mm to 20 mm, 2 mm to 30 mm, 2 mm to 40 mm, 2 mm to 50 mm,5 mm to 10 mm, 5 mm to 15 mm, 5 mm to 20 mm, 5 mm to 30 mm, 5 mm to 40mm, 5 mm to 50 mm, 10 mm to 15 mm, 10 mm to 20 mm, 10 mm to 30 mm, 10 mmto 40 mm, 10 mm to 50 mm, 15 mm to 20 mm, 15 mm to 30 mm, 15 mm to 40mm, 15 mm to 50 mm, 20 mm to 30 mm, 20 mm to 40 mm, 20 mm to 50 mm, 30mm to 40 mm, 30 mm to 50 mm, and 40 mm to 50 mm). In some embodiments,the distance between two hollow needles in an array of hollow needles isless than about 15 mm. The minimum distance may correspond to theminimal size of an array pattern, while the maximum distance maycorrespond to the maximum size of an array pattern.

Array patterns of different sizes and geometries may be generated basedon the area of treatment and the skin condition being treated. Arraypatterns may also be generated for compatibility with actuationmechanisms and control electronics of a given apparatus. Alternatively,actuation mechanisms and control electronics of an apparatus may beselected for compatibility with a desired array pattern size and/orgeometry. For example, a long, linear array pattern may be generatedusing a translating mechanism with driving wheels, while a large,rectangular array may be generated using an x- and/or y-actuator todrive the hollow needle(s) across the skin.

In any of the apparatuses, one or more hollow needles may be configuredto provide from about 10 to about 10000 cored tissue portions or moreper cm² area (e.g., 10 to 50, 10 to 100, 10 to 200, 10 to 300, 10 to400, 10 to 500, 10 to 600, 10 to 700, 10 to 800, 10 to 900, 10 to 1000,10 to 2000, 10 to 4000, 10 to 6000, 10 to 8000, 10 to 10000, 50 to 100,50 to 200, 50 to 300, 50 to 400, 50 to 500, 50 to 600, 50 to 700, 50 to800, 50 to 900, 50 to 1000, 50 to 2000, 50 to 4000, 510 to 6000, 50 to8000, 50 to 10000, 100 to 200, 100 to 300, 100 to 400, 100 to 500, 100to 600, 100 to 700, 100 to 800, 100 to 900, 100 to 1000, 100 to 2000,100 to 4000, 100 to 6000, 100 to 8000, 100 to 10000, 200 to 300, 200 to400, 200 to 500, 200 to 600, 200 to 700, 200 to 800, 200 to 900, 200 to1000, 200 to 2000, 200 to 4000, 200 to 6000, 200 to 8000, 200 to 10000,300 to 400, 300 to 500, 300 to 600, 300 to 700, 300 to 800, 300 to 900,300 to 1000, 300 to 2000, 300 to 4000, 300 to 6000, 300 to 8000, 300 to10000, 400 to 500, 400 to 600, 400 to 700, 400 to 800, 400 to 900, 400to 1000, 400 to 2000, 400 to 4000, 400 to 6000, 400 to 8000, 400 to10000, 500 to 600, 500 to 700, 500 to 800, 500 to 900, 500 to 1000, 500to 2000, 500 to 4000, 500 to 6000, 500 to 8000, 500 to 10000, 600 to700, 600 to 800, 600 to 900, 600 to 1000, 600 to 2000, 600 to 4000, 600to 6000, 600 to 8000, 600 to 10000, 700 to 800, 700 to 900, 700 to 1000,700 to 2000, 700 to 4000, 700 to 6000, 700 to 8000, 700 to 10000, 800 to900, 800 to 1000, 800 to 2000, 800 to 4000, 800 to 6000, 800 to 8000,800 to 10000, 900 to 1000, 900 to 2000, 900 to 4000, 900 to 6000, 900 to8000, 900 to 10000, 1000 to 2000, 1000 to 4000, 1000 to 6000, 1000 to8000, 1000 to 10000, 2000 to 4000, 2000 to 6000, 2000 to 8000, 2000 to10000, 4000 to 6000, 4000 to 8000, 4000 to 10000, 6000 to 8000, 6000 to10000, and 8000 to 10000 tissue portions per cm² area) of the skinregion to which the apparatus is applied (e.g., the treatment area).

Base Unit and User Interface

An apparatus of the invention may be in communication with a base unit,which may include, e.g., a user interface, a power supply, controlelectronics, mechanisms to drive operation of the apparatus, and othercomponents. The base unit may feature a computer, which may beprogrammed to operate and/or control any or all aspects of an apparatusof the invention.

A user interface in the base unit may include buttons, keys, switches,toggles, spin-wheels, screens, touch screens, keyboards, cursors, dials,indicators, displays, and/or other components. The user interface may beconfigured to indicate proper couplings and attachments of the supportbase (e.g., support base 11), the z-actuator (e.g., a voice coil;z-actuator 12), the tissue removal tool (e.g., a piston) (e.g., tissueremoval tool 13), the hollow needle(s) (e.g., hollow needle 14), theaspiration tube (e.g., aspiration tube 15), the trap (e.g., trap 16),the pressure generating source (e.g., a vacuum pump (e.g., pressuregenerating source 17), and/or scaffold 18 to form the needle assembly(e.g., needle assembly 10), charged and/or powered status of theapparatus, the mode and/or position of hollow needle(s), the applicationof low or high pressure, actuation of apparatus components, and/or otheruseful indicia. The user interface may be configured to provideinformation about the number and kind of hollow needle(s) of theapparatus, the treatment area, the treatment coverage (e.g., arealfraction of skin surface area removed), the arrangement of the hollowneedle(s), the potential depth of penetration by the hollow needle(s),the mechanism or mode of operation, use count of the hollow needle(s),and other useful information. The user interface may allow adjustment ofparameters and/or operation mode, application of high or low pressure,and/or activation of penetration into the skin by the hollow needle(s).The user interface may also be configured to transmit and/or receiveinformation from another unit. For example, user actions at a userinterface on the apparatus may be reflected by a user interface of thebase unit, or vice versa.

The base unit may include buttons, keys, switches, toggles, spin-wheels,and/or other activation mechanisms to allow adjustment of parametersand/or operation mode, application of high or low pressure, penetrationinto the skin by the hollow needle(s), and/or powering on or off of thebase unit and/or pressure generating source. These components may beintegrated into the user interface of the base unit.

The base unit may further include electronics to control operation ofthe apparatus, pressure generating source, and/or other componentscouple to the apparatus. For example, the base unit may include one ormore microcontrollers, programmable logic, discrete elements, and/orother components. The base unit may further have one or more powersupplies. Power supplies may include batteries, alternators, generators,and/or other components. The base unit may be configured to allowconversion of main power to DC for system operation, for example. Insome embodiments, the base unit has a battery charging station for usewith a battery-powered apparatus.

The base unit may include a user interface that indicates, e.g., thatthe hollow needle is properly installed in the needle assembly, that theneedle assembly is properly coupled to the actuation unit, that theapparatus is charged or otherwise powered (e.g., the amount of batterylife remaining), that the hollow needle is in an extended or retractedposition, that a pressure generating source is coupled to the apparatus,the fill level of a trap for collecting cored tissue portions, and/orother useful information. User interface may include information aboutthe apparatus, such as the number of hollow needle(s) of the apparatus,the arrangement of the hollow needle(s), the potential depth of tissuepenetration by the hollow needle(s), the mechanism or mode of operation,and/or other useful information. User interface may include buttons,keys, switches, toggles, spin-wheels, LED displays, and/or touch screensthat allow the user to observe and change various parameters orconfigurations during operation of the apparatus, to activate thepressure generating source, and/or to initiate penetration into the skinby the hollow needle(s). User interface may also be configured totransmit and/or receive information from another unit, such as acomputer.

Additional Components

Additional components, such as a camera and/or viewing station, may becoupled to an apparatus of the invention. A camera may be used to imagea treatment area before, during, or after treatment. In someembodiments, a camera may be disposed in or on the apparatus. The cameramay transmit signal to a viewing station, such as a computer, that maybe disposed in the line of sight of the device operator. The image orimages transmitted by the camera to the viewing station (e.g., acomputer) may be processed by a visualization software. Thevisualization software may be capable of calculating a hole densitywithin a treatment area (e.g., the number of holes generated per unitarea). The image or images transmitted by the camera to the viewingstation (e.g., a computer) may assist the operator in treating the skin.A fluid system may be coupled to an apparatus of the invention tofacilitate cleaning of the skin, e.g., with saline or a sterilizingsolution.

The hollow needles, needle assemblies, actuation units, apparatuses,kits, and methods of the invention may be used in combination with amedical record system, e.g., a Computerized Patient Record System(CPRS), and/or a graphic user interface (GUI). The graphic userinterface may provide information regarding various parameters of thetreatment site of the patient, such as the size of the array pattern andthe number of holes to be selected for in each treatment site.

Materials

The hollow needles, needle assemblies, actuation units, apparatuses,kits, and methods of the invention can include any useful materials. Forexample, the needle assembly may include and/or be formed from anyuseful polymer or plastic. Such materials may include alginate, benzylhyaluronate, carboxymethylcellulose, cellulose acetate, chitosan,collagen, dextran, epoxy, gelatin, hyaluronic acid, hydrocolloids, nylon(e.g., nylon 6 or PA6), pectin, poly (3-hydroxyl butyrate-co-poly(3-hydroxyl valerate), polyalkanes, polyalkene, polyalkynes,polyacrylate (PA), polyacrylonitrile (PAN), polybenzimidazole (PBI),polycarbonate (PC), polycaprolactone (PCL), polyester (PE), polyethyleneglycol (PEG), polyethylene oxide (PEO), PEO/polycarbonate/polyurethane(PEO/PC/PU), poly(ethylene-co-vinyl acetate) (PEVA), PEVA/polylacticacid (PEVA/PLA), polyethylene, polypropylene, poly (ethyleneterephthalate) (PET), PET/poly (ethylene naphthalate) (PET/PEN)polyglactin, polyglycolic acid (PGA), polyglycolic acid/polylactic acid(PGA/PLA), polyimide (PI), polylactic acid (PLA), poly-L-lactide (PLLA),PLLA/PC/polyvinylcarbazole (PLLA/PC/PVCB), poly (β-malicacid)-copolymers (PMLA), polymethacrylate (PMA), poly (methylmethacrylate) (PMMA), polystyrene (PS), polyurethane (PU), poly (vinylalcohol) (PVA), polyvinylcarbazole (PVCB), polyvinyl chloride (PVC),polyvinylidenedifluoride (PVDF), polyvinylpyrrolidone (PVP), silicone,rayon, polytetrafluoroethylene (PTFE), polyether ether ketone (PEEK), orcombinations thereof. Polymers and/or plastics of the invention may becomposite materials in which additives to the polymers and/or plastics,such as ceramics or particles, alter the mechanical properties.

Elements of the invention (e.g., all or a portion of the apparatus, suchas all or a portion of the needle assembly, the actuation unit, or othercomponents) may also include and/or be formed from any useful metal ormetal alloy. For example, in some embodiments, a hollow needle may be ametallic needle. Metals and alloys featured in the invention includestainless steel; titanium; a nickel-titanium (NiTi) alloy; anickel-titanium-niobium (NiTiNb) alloy; a nickel-iron-gallium (NiFeGa)alloy; a nickel-manganese-gallium (NiMnGa) alloy; acopper-aluminum-nickel (CuAlNi) allow; a copper-zinc (CuZn) alloy; acopper-tin (CuSn) alloy; a copper-zinc-aluminum (CuZnAl) alloy; acopper-zinc-silicon (CuZnSi) alloy; a copper-zinc-tin (CuZnSn) alloy; acopper-manganese alloy; a gold-cadmium (AuCd) alloy; a silver-cadmium(AgCd) alloy; an iron-platinum (FePt) alloy; an iron-manganese-silicon(FeMnSi) alloy; a cobalt-nickel-aluminum (CoNiAl) alloy; acobalt-nickel-gallium (CoNiGa) alloy; or a titanium-palladium (TiPd)alloy. Elements of the invention may also include and/or be formed fromglass. For example, an apparatus of the invention may include one ormore glass hollow needles.

The hollow needles, needle assemblies, actuation units, apparatuses,kits, and methods of the invention may contain one or more adhesives. Anadhesive may be located on a surface, between elements, or otherwiseadhered to an element of the invention. Useful adhesives include abiocompatible matrix (e.g., those including at least one of collagen(e.g., a collagen sponge), low melting agarose (LMA), polylactic acid(PLA), and/or hyaluronic acid (e.g., hyaluranon); a photosensitizer(e.g., Rose Bengal, riboflavin-5-phosphate (R-S-P), methylene blue (MB),N-hydroxypyridine-2-(1H)-thione (N-HTP), a porphyrin, or a chlorin, aswell as precursors thereof); a photochemical agent (e.g., 1,8naphthalimide); a synthetic glue (e.g., a cyanoacrylate adhesive, apolyethylene glycol adhesive, or a gelatin-resorcinol-formaldehydeadhesive); a biologic sealant (e.g., a mixture of riboflavin-5-phosphateand fibrinogen, a fibrin-based sealant, an albumin-based sealant, or astarch-based sealant); or a hook or loop and eye system (e.g., as usedfor Velcro®). In some embodiments, the adhesive is biodegradable.

The adhesive may be a pressure-sensitive adhesive (PSA). The propertiesof pressure sensitive adhesives are governed by three parameters: tack(initial adhesion), peel strength (adhesion), and shear strength(cohesion). Pressure-sensitive adhesives can be synthesized in severalways, including solvent-borne, water-borne, and hot-melt methods. Tackis the initial adhesion under slight pressure and short dwell time anddepends on the adhesive's ability to wet the contact surface. Peelstrength is the force required to remove the PSA from the contactsurface. The peel adhesion depends on many factors, including the tack,bonding history (e.g. force, dwell time), and adhesive composition.Shear strength is a measure of the adhesive's resistance to continuousstress. The shear strength is influenced by several parameters,including internal adhesion, cross-linking, and viscoelastic propertiesof the adhesive. Permanent adhesives are generally resistant todebonding and possess very high peel and shear strength.Pressure-sensitive adhesives may include natural rubber, syntheticrubber (e.g., styrene-butadiene and styrene-ethylene copolymers),polyvinyl ether, polyurethane, acrylic, silicones, and ethylene-vinylacetate copolymers. A copolymer's adhesive properties can be altered byvarying the composition (via monomer components) changing the glasstransition temperature (Tg) or degree of cross-linking. In general, acopolymer with a lower Tg is less rigid and a copolymer with a higher Tgis more rigid. The tack of PSAs can be altered by the addition ofcomponents to alter the viscosity or mechanical properties. Pressuresensitive adhesives are further described in Czech et al.,“Pressure-Sensitive Adhesives for Medical Applications,” in Wide Spectraof Quality Control, Dr. Isin Akyar (Ed., published by InTech), Chapter17 (2011), which is hereby incorporated by reference in its entirety.

An apparatus, method, or kit may contain or be configured to deliver oneor more useful therapeutic agents. For example, the hollow needles ofthe apparatus of the invention may be configured to administer one ormore therapeutic agents to the skin. The hollow needles of the apparatusof the invention may be capable of creating direct channels or holes tothe local blood supply and local perfusion by removing cored tissueportions. The direct channels or holes may be used to deliver usefultherapeutic agents. Depending on the size (e.g., diameter and/or activelength) of the hollow needles, holes having different diameters and/orpenetration depths may be created. For example, hollow needles having alarge diameter (e.g., 18 gauge) and/or a long active length may be usedto create large and deep holes that may be used as delivery channels todeliver a large volume dose of therapeutic agents. In some embodiments,the holes may be plugged. In some embodiments, the holes may be coveredwith a dressing (e.g., a compressive or occlusive dressing) and/or aclosure (e.g., bandage, hemostats, sutures, or adhesives) to prevent thedelivered therapeutic agents from leaking out of the skin and/or tomaintain moisture of the treated skin area. Delivery of usefultherapeutic agents through the holes created by the hollow needles ofthe apparatus may provide precise control of dosing of the therapeuticagents.

Examples of useful therapeutic agents include one or more growth factors(e.g., vascular endothelial growth factor (VEGF), platelet-derivedgrowth factor (PDGF), transforming growth factor beta (TGF-β),fibroblast growth factor (FGF), epidermal growth factor (EGF), andkeratinocyte growth factor); one or more stem cells (e.g., adiposetissue-derived stem cells and/or bone marrow-derived mesenchymal stemcells); one or more skin whitening agents (e.g., hydroquinone); one ormore vitamin A derivatives (e.g., tretinoin), one or more analgesics(e.g., paracetamol/acetaminophen, aspirin, a non-steroidalantiinflammatory drug, as described herein, a cyclooxygenase-2-specificinhibitor, as described herein, dextropropoxyphene, co-codamol, anopioid (e.g., morphine, codeine, oxycodone, hydrocodone,dihydromorphine, pethidine, buprenorphine, tramadol, or methadone),fentanyl, procaine, lidocaine, tetracaine, dibucaine, benzocaine,p-butylaminobenzoic acid 2-(diethylamino) ethyl ester HCl, mepivacaine,piperocaine, dyclonine, or venlafaxine); one or more antibiotics (e.g.,cephalosporin, bactitracin, polymyxin B sulfate, neomycin, bismuthtribromophenate, or polysporin); one or more antifungals (e.g.,nystatin); one or more antiinflammatory agents (e.g., a non-steroidalantiinflammatory drug (NSAID, e.g., ibuprofen, ketoprofen, flurbiprofen,piroxicam, indomethacin, diclofenac, sulindac, naproxen, aspirin,ketorolac, or tacrolimus), a cyclooxygenase-2-specific inhibitor (COX-2inhibitor, e.g., rofecoxib (Vioxx®), etoricoxib, and celecoxib(Celebrex®)), a glucocorticoid agent, a specific cytokine directed at Tlymphocyte function), a steroid (e.g., a corticosteroid, such as aglucocorticoid (e.g., aldosterone, beclometasone, betamethasone,cortisone, deoxycorticosterone acetate, dexamethasone, fludrocortisoneacetate, hydrocortisone, methylprednisolone, prednisone, prednisolone,or triamcinolone) or a mineralocorticoid agent (e.g., aldosterone,corticosterone, or deoxycorticosterone)), or an immune selectiveantiinflammatory derivative (e.g., phenylalanine-glutamine-glycine (FEG)and its D-isomeric form (feG))); one or more antimicrobials (e.g.,chlorhexidine gluconate, iodine (e.g., tincture of iodine,povidone-iodine, or Lugol's iodine), or silver, such as silver nitrate(e.g., as a 0.5% solution), silver sulfadiazine (e.g., as a cream), orAg⁺ in one or more useful carriers (e.g., an alginate, such as Acticoat®including nanocrystalline silver coating in high density polyethylene,available from Smith & Nephew, London, U.K., or Silvercel® including amixture of alginate, carboxymethylcellulose, and silver coated nylonfibers, available from Systagenix, Gatwick, U.K.; a foam (e.g.,Contreet® Foam including a soft hydrophilic polyurethane foam andsilver, available from Coloplast A/S, Humlebk, Denmark); a hydrocolloid(e.g., Aquacel® Ag including ionic silver and a hydrocolloid, availablefrom Conva Tec Inc., Skillman, N.J.); or a hydrogel (e.g., Silvasorb®including ionic silver, available from Medline Industries Inc.,Mansfield, Mass.)); one or more antiseptics (e.g., an alcohol, such asethanol (e.g., 60-90%), 1-propanol (e.g., 60-70%), as well as mixturesof 2-propanol/isopropanol; boric acid; calcium hypochlorite; hydrogenperoxide; manuka honey and/or methylglyoxal; a phenol (carbolic acid)compound, e.g., sodium 3,5-dibromo-4-hydroxybenzene sulfonate,trichlorophenylmethyl iodosalicyl, or triclosan; a polyhexanidecompound, e.g., polyhexamethylene biguanide (PHMB); a quaternaryammonium compound, such as benzalkonium chloride (BAC), benzethoniumchloride (BZT), cetyl trimethylammonium bromide (CTMB), cetylpyridiniumchloride (CPC), chlorhexidine (e.g., chlorhexidine gluconate), oroctenidine (e.g., octenidine dihydrochloride); sodium bicarbonate;sodium chloride; sodium hypochlorite (e.g., optionally in combinationwith boric acid in Dakin's solution); or a triarylmethane dye (e.g.,Brilliant Green)); one or more antiproliferative agents (e.g.,sirolimus, tacrolimus, zotarolimus, biolimus, or paclitaxel); one ormore emollients; one or more hemostatic agents (e.g., collagen, such asmicrofibrillar collagen, chitosan, calcium-loaded zeolite, cellulose,anhydrous aluminum sulfate, silver nitrate, potassium alum, titaniumoxide, fibrinogen, epinephrine, calcium alginate, poly-N-acetylglucosamine, thrombin, coagulation factor(s) (e.g., II, V, VII, VIII,IX, X, XI, XIII, or Von Willebrand factor, as well as activated formsthereof), a procoagulant (e.g., propyl gallate), an anti-fibrinolyticagent (e.g., epsilon aminocaproic acid or tranexamic acid), and thelike); one or more procoagulative agents (e.g., any hemostatic agentdescribed herein, desmopressin, coagulation factor(s) (e.g., II, V, VII,VIII, IX, X, XI, XIII, or Von Willebrand factor, as well as activatedforms thereof), procoagulants (e.g., propyl gallate), antifibrinolytics(e.g., epsilon aminocaproic acid), and the like); one or moreanticoagulative agents (e.g., heparin or derivatives thereof, such aslow molecular weight heparin, fondaparinux, or idraparinux; ananti-platelet agent, such as aspirin, dipyridamole, ticlopidine,clopidogrel, or prasugrel; a factor Xa inhibitor, such as a directfactor Xa inhibitor, e.g., apixaban or rivaroxaban; a thrombininhibitor, such as a direct thrombin inhibitor, e.g., argatroban,bivalirudin, dabigatran, hirudin, lepirudin, or ximelagatran; or acoumarin derivative or vitamin K antagonist, such as warfarin(coumadin), acenocoumarol, atromentin, phenindione, or phenprocoumon);one or more immune modulators, including corticosteroids andnon-steroidal immune modulators (e.g., NSAIDS, such as any describedherein); one or more proteins; and/or one or more vitamins (e.g.,vitamin A, C, and/or E). One or more of botulinum toxin, fat (e.g.autologous), hyaluronic acid, a collagen-based filler, or other fillermay also be administered to the skin. Platelet rich plasma may also beadministered to the skin. One or more therapeutic agents describedherein may be formulated as a depot preparation. In general, depotpreparations are typically longer acting than non-depot preparations. Insome embodiments, depot preparations are prepared using suitablepolymeric or hydrophobic materials (for example an emulsion in anacceptable oil) or ion exchange resins, or as sparingly solublederivatives, for example, as a sparingly soluble salt.

A therapeutic agent may include anticoagulative and/or procoagulativeagents. For instance, by controlling the extent of bleeding and/orclotting in treated skin regions, a skin tightening effect may be moreeffectively controlled. Thus, in some embodiments, the methods anddevices herein include or can be used to administer one or moreanticoagulative agents, one or more procoagulative agents, one or morehemostatic agents, one or more fillers, or combinations thereof. Inparticular embodiments, the therapeutic agent controls the extent ofbleeding and/or clotting in the treated skin region, including the useone or more anticoagulative agents (e.g., to inhibit clot formationprior to skin healing or slit/hole closure) and/or one or morehemostatic or procoagulative agents.

Configurations

An apparatus of the invention may include a variety of components indifferent configurations. For example, an apparatus may include one ormore hollow needles, a pressure generating source, a tissue removal tool(e.g., a piston), an aspiration tube, a trap for collecting wastematerials (e.g., cored tissue portions), a support base, and anactuation unit (e.g., an actuation unit including an x-, y-, and/orz-actuator). One or more hollow needles, a pressure generating source, atissue removal tool (e.g., a piston), an aspiration tube, a trap forcollecting waste materials (e.g., cored tissue portions), a supportbase, and/or a z-actuator may be detachably connected to form a needleassembly (e.g., needle assembly 10 shown in FIGS. 1A-1F). Accordingly,an apparatus may include a needle assembly and an actuation unit. Thetrap may be disposed in the aspiration tube, in the hollow needle, or ina separate module disposed between the hollow needle and the z-actuatoror external to the apparatus. Similarly, a pressure generating source(e.g., a vacuum pump) may be disposed external to other components ormay be integrated into, e.g., the aspiration tube. Mechanisms foractuation, translation, and/or position detection; control electronics;and/or user interface may be included in the apparatus or external tothe apparatus. These configurations facilitate the sterilization of theapparatus as needed for patient treatment.

FIGS. 1A-1F are schematic illustrations showing a possible configurationof needle assembly 10 including support base 11, z-actuator (e.g., avoice coil) 12, tissue removal tool (e.g., a piston) 13, hollow needle14, aspiration tube 15, trap 16, pressure generating source (e.g., avacuum pump) 17, and scaffold 18. In this configuration, trap 16 isinstalled between pressure generating source (e.g., a vacuum pump) 17and aspiration tube 15. Trap 16, such as a stainless steel sterilizinggrade filter membrane (Mott Corporation), can be used to prevent coredtissue portions from entering pressure generating source (e.g., a vacuumpump) 17. Trap 16 may be detached and removed for cleaning and/or to bereplaced. Hollow needle 14 is in communication with support base 11,z-actuator (e.g., a voice coil) 12, and tissue removal tool (e.g., apiston) 13. Z-actuator (e.g., a voice coil) 12 causes translation ofhollow needle 14 along its longitudinal axis and insertion into andwithdrawal of hollow needle 14 from the skin. The needle assembly of theapparatus may also be digitally controlled (e.g., at a user interface).As such, operation of the apparatus may be entirely or almost entirelycontrollable by features of the apparatus.

Treatment of a region of skin of a patient may proceed by supplyingpower to the apparatus, preparing the skin region for treatment (e.g.,sterilizing and/or positioning the skin), placing a hollow needle (e.g.,hollow needle 14) of the apparatus upon the skin in the treatmentregion, and activating the mechanism (e.g., z-actuator) that drivespenetration of hollow needle into the skin. As the hollow needle iswithdrawn from the skin, it is in communication and contact with thetissue removal tool (e.g., a piston; tissue removal tool 13), whichslides into the lumen and pushes the cored tissue portion in the lumenof the hollow needle (e.g., hollow needle 14) towards the needle tip(e.g., needle tip 18) as the hollow needle continues to move upward. Theoperator may activate the pressure generating source (e.g., a vacuumpump; pressure generating source 17) to remove cored tissue portion fromthe needle tip. The activation of the pressure generating source may beautomatically trigged by the hollow needle (e.g., hollow needle 14) whenthe hollow needle is in its uppermost position. The cored tissue portionis aspirated into the aspiration tube (e.g., aspiration tube 15) asvacuum is applied and collects at the trap (e.g., trap 16) between theaspiration tube and the pressure generating source (e.g., a vacuumpump). Application of vacuum may be ceased prior to translation of thehollow needle to an adjacent skin region for further treatment. Theprocess may be repeated until the entire skin region of interest hasbeen treated, at which point the hollow needle (e.g., hollow needle 14)and/or the entire needle assembly (e.g., needle assembly 10) can bedetached from the apparatus via a quick-release mechanism, the hollowneedle (e.g., hollow needle 14) and/or the entire needle assembly (e.g.,needle assembly 10) disposed of or replaced, and the other components ofthe apparatus sterilized as needed. Such treatment may provide aplurality of cored tissue portions with dimensions, geometries, andother characteristics corresponding to the dimensions, geometries, andother characteristics of the hollow needle. For example, a hollow needleinserted about 2 mm into the skin may provide a tissue portion having adepth or length of about 2 mm.

In an alternative configuration, an apparatus of the invention mayintegrate a miniature pressure generating source (e.g., a vacuum pump)into the needle assembly of the apparatus. In this instance, theminiature pressure generating source (e.g., a vacuum pump) is in directcommunication with the hollow needle (e.g., the proximal end of thehollow needle). A cored tissue portion inside the lumen of the hollowneedle may be aspirated upward through the hollow needle by applyingvacuum. A trap may be installed between the hollow needle and theminiature pressure generating source (e.g., a vacuum pump) to collectthe cored tissue portion and prevent the cored tissue portion fromentering the miniature pressure generating source (e.g., a vacuum pump).In this instance, the cored tissue portion in the lumen is directlyaspirated upward through the hollow needle.

The pressure generating source (e.g., a vacuum pump) may be part of theneedle assembly of the apparatus (e.g., attached to the aspiration tube(if present)) or external to the apparatus; for example, the vacuumsource may be a medical or house vacuum source. Alternatively, thevacuum source may be a pump, such as a scroll, momentum transfer,rotary, diffusion, or diaphragm pump. The apparatus may further includea power supply, control electronics, and/or actuation, translation,and/or position detection mechanisms.

The apparatus may be charged by either removing the batteries from theirholder, e.g., to be charged in a battery charging unit, or by placingthe apparatus in an external battery charging station. The apparatusand/or base unit may also include components that allow for wirelesscommunication therebetween.

Kits

The invention also features kits for cosmetic resurfacing of the skintissue. In some embodiments, kits may include one or more hollowneedles. The kits may also include, either alone or with the one or morehollow needles, other components of a needle assembly of the apparatus(e.g., a support base (e.g., support base 11), a z-actuator (e.g., avoice coil; z-actuator 12), a tissue removal tool (e.g., tissue removaltool (e.g., a piston) 13), an aspiration tube (e.g., aspiration tube15), a trap (e.g., trap 16), a pressure generating source (e.g.,pressure generating source (e.g., a vacuum pump) 17), and/or a scaffold(e.g., scaffold 18)), an actuation unit including an x- and y-actuators(e.g., actuation unit 151), and/or a cover (e.g., cover 161). The one ormore hollow needles, the entire needle assembly, and/or components ofthe needle assembly in a kit may be configured to be detachably attachedto the apparatus. The hollow needle(s) may be configured to be incommunication with a pressure generating source (e.g., a vacuum pump).In some embodiments, kits may be packaged with the hollow needle(s) insterile form and with instructions for applying the hollow needle(s) tothe needle assembly of an apparatus of the invention and/or withinstructions for applying the needle assembly to the actuation unit ofthe apparatus of the invention. In some embodiments, kits may bepackaged with the entire needle assembly in sterile form and withinstructions for applying the needle assembly to the actuation unit ofan apparatus of the invention. Kits may also include one or morereplacement hollow needles and/or one or more replacement components ofthe needle assembly. Kits may also include entire needle assemblies asreplacement parts.

Kits of the invention may include additional components, such as a trapfor collecting waste materials (e.g., cored tissue portions); a pressuregenerating source (e.g., a vacuum pump); mechanisms for actuation,translation, and position detection (e.g., one or more voice coil (VC),pneumatic, electromagnetic, and/or piezoelectric actuators; drivingwheels; and/or a camera); and a base unit having a user interface. Inaddition, kits of the invention may include any other useful components,such as instructions on how to use the hollow needle(s), the needleassembly, the actuation unit, and/or the apparatus, one or moretherapeutic agents (e.g., any described herein, such as ananticoagulative and/or procoagulative agent, and optionally incombination with a useful dispenser for applying the therapeutic agent,such as a brush, spray, film, ointment, cream, lotion, or gel), one ormore wound cleansers (e.g., including any antibiotic, antimicrobial, orantiseptic, such as those described herein, in any useful form, such asa brush, spray, film, ointment, cream, lotion, or gel), one or moredressings (e.g., compressive or occlusive dressings), one or moreclosures (e.g., bandage, hemostats, sutures, or adhesives), one or moredebriding agents, one or more adhesives (e.g., any described herein),one or more cosmetics (e.g., as described herein), and/or other suitableor useful materials.

Kits of the invention may include any of the components provided herein(e.g., hollow needle(s), a trap, a pressure generating source, a tissueremoval tool (e.g., a piston), an aspiration tube, and/or a z-actuator)in any number. Kits may also have or be designed to have any of theconfigurations described herein.

Method for Cosmetic Skin Resurfacing

Any of the hollow needles, needle assemblies, actuation units,apparatuses, kits, and methods of the invention may be used for cosmeticskin resurfacing of the skin tissue by removing skin tissue portions.The hollow needles, needle assemblies, actuation units, apparatuses,kits, and methods of the invention can be applied to treat one or moreskin regions. In particular embodiments, these regions are treated withone or more procedures to improve skin appearance and to rejuvenateskin. In preferred embodiments, the hollow needles, needle assemblies,actuation units, apparatuses, kits, and methods described herein can beuseful for skin tightening, e.g., reducing skin laxity (e.g., loose orsagging skin or other skin irregularities). In other embodiments, thehollow needles, needle assemblies, actuation units, apparatuses, kits,and methods herein can be useful for removal of, e.g., pigment, hairfollicles, and/or vessels in the skin, and/or for treating acne,allodynia, blemishes, ectopic dermatitis, hyperpigmentation, hyperplasia(e.g., lentigo or keratosis), loss of translucency, loss of elasticity,melasma (e.g., epidermal, dermal, or mixed subtypes), photodamage,rashes (e.g., erythematous, macular, papular, and/or bullousconditions), psoriasis, rhytides (or wrinkles, e.g., lateral canthallines (“crow's feet”), age-related rhytides, sun-related rhytides, orheredity-related rhytides), sallow color, scar contracture (e.g.,relaxation of scar tissue), scarring (e.g., due to acne, surgery, orother trauma), skin aging, skin contraction (e.g., excessive tension inthe skin), skin irritation/sensitivity, striae (or stretch marks),tattoo removal, vascular lesions (e.g., angioma, erythema, hemangioma,papule, port wine stain, rosacea, reticular vein, or telangiectasia), orany other unwanted skin irregularities. The hollow needles, needleassemblies, actuation units, apparatuses, kits, and methods describedherein may also be used to penetrate skin and trigger biologicalresponses that may contribute to new skin tissue formation and tissueresurfacing and remodeling.

Such skin treatments may be applied to any part or parts of the body,including the face (e.g., eyelid, cheeks, chin, forehead, lips, ornose), neck, chest (e.g., as in a breast lift), arms, hands, legs,abdomen, and/or back. Accordingly, the hollow needles, needleassemblies, actuation units, apparatuses, kits, and methods of theinvention can be configured to be useful for treatment of regions of thebody with different sizes and geometries. For example, arrays of hollowneedles of different sizes, geometries, and arrangements may be includedin a kit of the invention to allow for treatment of both facial (e.g.,with tips having small arrays of regular or irregular geometries) andabdominal regions (e.g., with tips having large arrays of regulargeometries). In some embodiments, such arrangements and configurationscan be in one or more rows or in a semi-random spatial distribution. Inother embodiments, arrangements of hollow needles can include any usefulshape (e.g., linear, curved, or stellate), size, geometry, depth, and/orother characteristics. Alternatively, an apparatus of the invention caninclude a single hollow needle and the apparatus can be used torepeatedly remove skin tissue in an array pattern forming one or morerows, random or semi-random patterns, or other patterns.

Treatment methods may involve forming a plurality of holes in the skinby contacting one or more hollow needles to the skin of a subject andremoving the cored tissue portions from the skin. Penetration into theskin by the hollow needle(s) create holes and so effectively reducetissue volume and/or improve tissue quality upon healing. For example,forming a series of cored tissue portions (e.g., removal of about 20% ofthe total skin area) and corresponding holes in a high laxity skinregion and optionally subsequent compression of the skin region to closethe holes may promote the growth of new skin (e.g., improved tissue).Healing of the tissue under a dressing (e.g., a compressive or occlusivedressing) allows for the existing tissue to span the gap introduced bythe removal of cored tissue portions, thereby reducing the skin volumeand area (e.g., by tightening the skin). A dressing (e.g., a compressiveor occlusive dressing) may also help to maintain moisture of the treatedskin area and/or to prevent delivered therapeutic agents from leakingout of the skin.

Any beneficial area or volumetric fraction of the skin region can beremoved. For example, between about 1% to about 65% (e.g., an arealfraction between about 0.01 to about 0.65, such as 0.01 to 0.65, 0.01 to0.6, 0.01 to 0.55, 0.01 to 0.5, 0.01 to 0.45, 0.01 to 0.4, 0.01 to 0.35,0.01 to 0.3, 0.01 to 0.25, 0.01 to 0.2, 0.01 to 0.15, 0.01 to 0.1, 0.01to 0.05, 0.03 to 0.65, 0.05 to 0.65, 0.07 to 0.65, 0.09 to 0.65, 0.1 to0.65, 0.15 to 0.65, 0.2 to 0.65, 0.25 to 0.65, 0.3 to 0.65, 0.35 to0.65, 0.4 to 0.65, 0.45 to 0.65, 0.5 to 0.65, 0.55 to 0.65, and 0.6 to0.65) of tissue in the treatment area may be removed. In someembodiments, between about 1% to about 5% (e.g., an areal fractionbetween about 0.01 to about 0.05, such as 0.01 to 0.05, 0.01 to 0.045,0.01 to 0.04, 0.01 to 0.035, 0.01 to 0.03, 0.01 to 0.025, 0.01 to 0.02,0.01 to 0.015, 0.015 to 0.05, 0.02 to 0.05, 0.025 to 0.05, 0.03 to 0.05,0.035 to 0.05, 0.04 to 0.05, and 0.045 to 0.05) of tissue in thetreatment area may be removed. In some embodiments, between about 2% toabout 3% (e.g., an areal fraction between about 0.02 to about 0.03, suchas 0.02 to 0.03, 0.02 to 0.028, 0.02 to 0.026, 0.02 to 0.024, 0.02 to0.022, 0.022 to 0.03, 0.024 to 0.03, 0.026 to 0.03, 0.028 to 0.03; e.g.,0.025) of tissue in the treatment area may be removed.

Tissue can be removed from the treatment region with various holedensity (e.g., the number of holes per unit area) corresponding to thenumber and geometry of hollow needle(s) of the apparatus used and thenumber of applications of the hollow needle(s) to the treatment region.Different hole densities may be desirable for different regions of skinand for different conditions and may be achieved using different hollowneedle(s). For example, 15 holes corresponding to the size of a 19 gaugeneedle and their corresponding cored tissue portions may be created in agiven treatment area by actuation of a single 19 gauge needle 15 times,or by actuating an array having five 19 gauge needles three times.Spacing the same number of holes further apart will result in a lowerhole density per unit area. For example, 15 holes may be created withina 0.5 mm by 0.3 mm region or within a 5 mm by 3 mm region. In particularembodiments, hollow needles, needle assemblies, actuation units,apparatuses, kits, and methods of the invention (e.g., any describedherein) are configured to provide from about 10 to about 10000 coredtissue portions per cm² area of the skin region (e.g., as describedherein). The array of holes created by removal of the skin tissueportions may be created in any beneficial pattern within the skinregion. For example, a higher density and/or smaller spacing of tissueportions and corresponding holes can be ablated in the skin in thecenter of a pattern or in thicker portions of the skin. A pattern may besemi-random or include one or more of staggered rows and/or blocks,parallel rows and/or blocks, a circular pattern, a spiral pattern, asquare or rectangular pattern, a triangular pattern, a hexagonalpattern, a radial distribution, or a combination of one or more suchpatterns. The pattern may arise from the use of one or more hollowneedles with one or more configurations and numbers of hollow needlesapplied in any ordered or disordered manner. Modifications to theaverage length, diameter, shapes, and/or other characteristics of one ormore hollow needles used to treat a skin region may also result in aspecific pattern of holes in the skin. Such patterns may be optimized topromote unidirectional, non-directional, or multidirectional contractionor expansion of skin (e.g., in the x-direction, y-direction,x-direction, x-y plane, y-z plane, x-z plane, and/or xyz-plane), such asby modifying the average length, depth, diameter, density, orientation,and/or spacing between hollow needles.

Any portion of the skin can be removed. Tissue portions created bypenetration into the skin with the hollow needle(s) may includeepidermal tissue, dermal tissue, subcutaneous fat, and/or cells ortissue proximal to the dermal/fatty layer boundary (e.g., stem cells).In some embodiments, a tissue portion may have a length that correspondsto the depth of penetration of the skin layer. In some embodiments, thedepth of penetration may be (i) into the dermal layer, (ii) through theentire dermal layer to the junction of the dermal layer and thesubcutaneous fat layer, or (iii) into the subcutaneous fat layer. Thetotal depth of the epidermal, dermal, and subcutaneous fat layers mayvary based on the region and age of the body being treated. In someinstances, the depth of the epidermal layer is between about 0.01 mm to0.2 mm, and/or the depth of the dermal layer is between about 0.3 mm to6.0 mm. In some embodiments, the total depth of the epidermal and dermallayers may be between about 0.3 mm and 6.2 mm, corresponding to apossible tissue portion having a length between about 0.3 mm and 6.2 mm(e.g., between about 0.3 mm and 0.6 mm, 0.3 mm and 0.9 mm, 0.3 mm and1.5 mm, 0.3 mm and 2.0 mm, 0.3 mm and 2.5 mm, 0.3 mm and 3.0 mm, 0.3 mmand 3.5 mm, 0.3 mm and 4.0 mm, 0.3 mm and 4.5 mm, 0.3 mm and 5.0 mm, 0.3mm and 5.5 mm, 0.3 mm and 6.0 mm, 0.3 mm and 6.2 mm, 0.6 mm and 0.9 mm,0.6 mm and 1.5 mm, 0.6 mm and 2.0 mm, 0.6 mm and 2.5 mm, 0.6 mm and 3.0mm, 0.6 mm and 3.5 mm, 0.6 mm and 4.0 mm, 0.6 mm and 4.5 mm, 0.6 mm and5.0 mm, 0.6 mm and 5.5 mm, 0.6 mm and 6.0 mm, 0.6 mm and 6.2 mm, 0.9 mmand 1.5 mm, 0.9 mm and 2.0 mm, 0.9 mm and 2.5 mm, 0.9 mm and 3.0 mm, 0.9mm and 3.5 mm, 0.9 mm and 4.0 mm, 0.9 mm and 4.5 mm, 0.9 mm and 5.0 mm,0.9 mm and 5.5 mm, 0.9 mm and 6.0 mm, 0.9 mm and 6.2 mm, 1.5 mm and 2.0mm, 1.5 mm and 2.5 mm, 1.5 mm and 3.0 mm, 1.5 mm and 3.5 mm, 1.5 mm and4.0 mm, 1.5 mm and 4.5 mm, 1.5 mm and 5.0 mm, 1.5 mm and 5.5 mm, 1.5 mmand 6.0 mm, 1.5 mm and 6.2 mm, 2.0 mm and 2.5 mm, 2.0 mm and 3.0 mm, 2.0mm and 3.5 mm, 2.0 mm and 4.0 mm, 2.0 mm and 4.5 mm, 2.0 mm and 5.0 mm,2.0 mm and 5.5 mm, 2.0 and 6.0 mm, 2.0 mm and 6.2 mm, 2.5 mm and 3.0 mm,2.5 mm and 3.5 mm, 2.5 mm and 4.0 mm, 2.5 mm and 4.5 mm, 2.5 mm and 5.0mm, 2.5 mm and 5.5 mm, 2.5 mm and 6.0 mm, 2.5 mm and 6.2 mm, 3.0 mm and3.5 mm, 3.0 mm and 4.0 mm, 3.0 mm and 4.5 mm, 3.0 mm and 5.0 mm, 3.0 mmand 5.5 mm, 3.0 and 6.0 mm, 3.0 mm and 6.2 mm, 3.5 mm and 4.0 mm, 3.5 mmand 4.5 mm, 3.5 mm and 5.0 mm, 3.5 mm and 5.5 mm, 3.5 and 6.0 mm, 3.5 mmand 6.2 mm, 4.0 mm and 4.5 mm, 4.0 mm and 5.0 mm, 4.0 mm and 5.5 mm, 4.0and 6.0 mm, 4.0 mm and 6.2 mm, 4.5 mm and 5.0 mm, 4.5 mm and 5.5 mm, 4.5and 6.0 mm, 4.5 mm and 6.2 mm, 5.0 mm and 5.5 mm, 5.0 mm and 6.0 mm, 5.0mm and 6.2 mm, 5.5 mm and 6.0 mm, 5.5 mm and 6.2 mm, or 6.0 mm and 6.2mm).

In some instances, it may be desirable to configure hollow needles,needle assemblies, actuation units, apparatuses, kits, and methods ofthe invention to provide one or more tissue portions that do not includesignificant amounts of subcutaneous tissue, or, in other instances, toprovide tissue portions that do include significant amounts ofsubcutaneous tissue. Electronic and/or physical mechanisms may be usedto control the depth of penetration into the skin by the hollowneedle(s) and the corresponding size of a cored tissue portion and hole.For example, an apparatus may include one or more one or more spacers asdescribed herein; one or more scroll wheels, buttons, dials, toggles, orother components to physically retract the hollow needle(s); az-actuation mechanism (e.g., a pneumatic, electromagnetic, orpiezoelectric actuator or a motor with a cam); and/or one or moresensors (e.g., force sensors, optical sensors, laser fibers,photodetectors, and/or position sensors) in communication with one ormore hollow needles, actuators, valves, pressure generating sources,and/or user interfaces to detect the position of hollow needle(s) and/orthe position of the apparatus relative to the treated skin portion.

EXAMPLES Example 1—Treatment of Skin Laxity in the Face Using a HollowNeedle with Two Prongs

An apparatus of the invention may be used to administer treatment to theskin of a subject. Treatment may be performed outside of an operatingroom environment, thereby minimizing the cost of treatment.

The apparatus used for treatment of the subject may be any of thosedescribed herein. For example, the apparatus may be that shown in anyone of FIGS. 16D-16I (e.g., apparatus 163 including actuation unit 151,needle assembly 10, and cover 161). For treatment of skin laxity in theface, a metallic, hollow needle with two prongs each having a bevelangle α of 30 degrees may be selected for application to a treatmentarea of about 4 mm by about 9 mm. The selected hollow needle may be a 24gauge needle and may be affixed to the needle assembly of the apparatusat its proximal end (e.g., away from the needle tip). The tip of eachprong of the hollow needle may be a sharp point (e.g., sharp point 51 asillustrated in FIG. 5A). The hollow needle may be configured topenetrate about 0.5 mm to about 2 mm (e.g., about 1 mm) into the skinand to remove an areal fraction of about 0.03 of skin tissue.

The skin area may first be sterilized, treated with chemicals, and/orotherwise prepared for treatment. The positioning mechanism disposed inthe apparatus may be applied to position the hollow needle to the areaof treatment. Treatment may proceed with the driving of the needle intoand out of the skin by activation of the z-actuator, driving the needlecontaining the cored tissue portion inside its lumen to be in contactwith the tissue removal tool (e.g., a piston), removal of cored tissueportion by activation of the vacuum pump coupled to the aspiration tubeand the trap, and translation of the hollow needle or the entireapparatus to an adjacent region for treatment. When sufficient tissuearea has been treated, the apparatus components may be powered off, theskin surface and/or holes are cleaned and/or flushed with fluid, andoptionally a compressive wound dressing applied to the skin to cause theholes to close. The trap may be disposed of, and other components of thesystem may be detached and sterilized.

The treatment may be rapid (e.g., less than 30 minutes), minimizingpatient downtime and allowing treatment to be carried out as anoutpatient procedure. Within days, a reduction in skin laxity and/orrhytides in the treatment area may be observed.

Example 2—Treatment of Skin Laxity in the Face Using a Hollow NeedleHaving an Edge

The hollow needle used in Example 1 may be replaced with a hollow needlehaving an edge. For example, the hollow needle used to treat skin laxityin the face may be a metallic, hollow needle with two prongs each havinga bevel angle α of 30 degrees. The hollow needle may be a 24 gaugeneedle and may be affixed to the needle assembly of the apparatus at itsproximal end (e.g., away from the needle tip). The tip of each prong ofthe hollow needle may be an edge (e.g., edge 52 as illustrated in FIG.5B). The hollow needle may be configured to penetrate about 0.5 mm toabout 2 mm (e.g., about 1 mm) into the skin and to remove an arealfraction of about 0.03 of skin tissue.

Example 3—Treatment of Skin Laxity in the Face Using a Hollow NeedleHaving a Flat Tip

The hollow needle used in Example 1 may be replaced with a hollow needlehaving a flat tip (e.g., a two dimensional flat tip). For example, thehollow needle used to treat skin laxity in the face may be a metallic,hollow needle with two prongs each having a bevel angle α of 30 degrees.The hollow needle may be a 24 gauge needle and may be affixed to theneedle assembly of the apparatus at its proximal end (e.g., away fromthe needle tip). The tip of each prong of the hollow needle may be aflat tip (e.g., flat tip 53 as illustrated in FIG. 5C). The hollowneedle may be configured to penetrate about 0.5 mm to about 2 mm (e.g.,about 1 mm) into the skin and to remove an areal fraction of about 0.03of skin tissue.

Other Embodiments

While the invention has been described in connection with specificembodiments thereof, it will be understood that it is capable of furthermodifications and this application is intended to cover any variations,uses, or adaptations of the invention following, in general, theprinciples of the invention and including such departures from thepresent disclosure come within known or customary practice within theart to which the invention pertains and may be applied to the essentialfeatures hereinbefore set forth.

All publications, patents, and patent applications are hereinincorporated by reference in their entirety to the same extent as ifeach individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by referencein its entirety.

Other embodiments are within the following claims.

1. (canceled)
 2. A needle assembly comprising: a hollow needle having alumen, a z-actuator configured to perform multiple actuation cycles,where each actuation cycle comprises: displacing the hollow needle toextend into at least the dermal layer, and withdrawing the hollow needlefrom the dermal layer, wherein a single actuation cycle takes from about5 milliseconds to about 50 milliseconds.
 3. The needle assemblyaccording to claim 2, wherein the z-actuator takes about 20 millisecondsto about 35 milliseconds to extend the hollow needle about 20millimeters to about 30 millimeters towards the dermal layer and thehollow needle extends into the dermal layer.
 4. The needle assemblyaccording to claim 2, wherein the z-actuator takes about 25 millisecondsto about 30 milliseconds to extend the hollow needle about 23millimeters into skin tissue.
 5. The needle assembly according to claim2, wherein the z-actuator takes about 25 milliseconds to about 35milliseconds to withdraw the hollow needle about 20 millimeters to about30 millimeters from a penetration depth in the skin tissue of about 20millimeters to about 30 millimeters.
 6. The needle assembly according toclaim 2, wherein the z-actuator takes about 30 milliseconds to withdrawthe hollow needle to a position about 23 millimeters away from thedermal layer.
 7. The needle assembly according to claim 2, wherein thez-actuator operates with an insertion force of about 0.5 Newtons toabout 20 Newtons.
 8. The needle assembly according to claim 2, whereinthe z-actuator operates with an insertion force of about 10 Newtons toabout 20 Newtons.
 9. The needle assembly according to claim 2, whereinthe hollow needle comprises at least a first prong.
 10. The needleassembly according to claim 9, wherein the hollow needle furthercomprises a second prong.
 11. The needle assembly according to claim 9,wherein an angle (α) between a lateral side of the first prong and alongitudinal axis of the hollow needle is between 5 degrees and 20degrees.
 12. The needle assembly according to claim 9, wherein an angle(α) between a lateral side of the first prong and a longitudinal axis ofthe hollow needle is less than 20 degrees.
 13. The needle assemblyaccording to claim 10, wherein an angle (α) between a lateral side ofthe second prong and a longitudinal axis of the hollow needle is between5 degrees and 20 degrees.
 14. The needle assembly according to claim 10,wherein an angle (α) between a lateral side of the second prong and alongitudinal axis of the hollow needle is less than 20 degrees.
 15. Theneedle assembly according to claim 2, wherein the needle assembly isconfigured to be detachably attached to an x- and/or y-actuator.
 16. Theneedle assembly according to claim 2, wherein portions of skin tissueremoved from the lumen of the hollow needle are tissue portions thatremain intact through the removal.
 17. The needle assembly according toclaim 2, further comprising an aspiration tube, wherein the aspirationtube is coupled to a trap.
 18. The needle assembly according to claim 2,further comprising a low pressure source, wherein the low pressuresource is a vacuum pump.
 19. The needle assembly according to claim 17,wherein the trap is configured to capture portions of skin tissue to bediscarded.
 20. The needle assembly according to claim 2, furthercomprising a spacer.
 21. The needle assembly according to claim 20,wherein the spacer is attached to a cover, wherein the spacer ispositioned between the cover and skin tissue, and wherein the spacer isconfigured to control the depth of insertion of the hollow needle. 22.The needle assembly according to claim 9, wherein an angle (α) between alateral side of the first prong and a longitudinal axis of the hollowneedle is 10 degrees.
 23. The needle assembly according to claim 10,wherein an angle (α) between a lateral side of the second prong and alongitudinal axis of the hollow needle is 10 degrees.